One 200 mg dose of the antibiotic doxycycline, taken as soon as possible and no later than 72 hours after oral, anal or vaginal sex. That’s doxyPEP (doxycycline post-exposure prophylaxis). It cuts the risk of syphilis and chlamydia sharply, and gonorrhea less reliably. The CDC’s June 2024 guidelines tell providers to offer it to gay, bisexual and other men who have sex with men (MSM) and to transgender women who had syphilis, chlamydia or gonorrhea in the past 12 months.
Across three large trials, the guidelines say, doxyPEP reduced “syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%.” Newer real-world data suggest the gonorrhea benefit is fading where resistant strains have spread. (More on that below.) DoxyPEP doesn’t prevent HIV, herpes, HPV or mpox. This guide explains the evidence. It isn’t individual medical advice, so talk with a health care provider about whether doxyPEP fits your sex life and health.
How to Take DoxyPEP: The 200 mg Dose
The CDC dose is 200 mg of doxycycline (any formulation) “once within 72 hours (not to exceed 200 mg per 24 hours) of oral, vaginal, or anal sex.” Sooner is better. That cap runs on a 24-hour clock rather than a calendar day, so a second round of sex the same night doesn’t mean a second dose.
Chicago’s Howard Brown Health, an LGBTQ+ health center with a dedicated doxyPEP service, teaches it as “3, 2, 1”: within 3 days, take 2 tablets (200 mg), just 1 time per day.
The CDC’s provider guidance has a few tips for sparing your throat and stomach:
| Do | Why |
|---|---|
| “Take doxy PEP with at least 8 ounces of water and food.” | Cuts nausea and irritation of the esophagus |
| “Do not lie down for one hour after taking doxycycline.” | Lowers the risk of esophagus irritation |
| Separate doses by at least 2 hours from dairy, antacids and calcium, iron or magnesium supplements | These block absorption |
| “Wear sunscreen or cover up” | Doxycycline makes skin more sun-sensitive |
Doxycycline is the CDC’s recommended treatment for chlamydia. A prevention dose still isn’t a treatment course. If you have symptoms or a positive test, you need proper testing and treatment.
Who the CDC Recommends DoxyPEP For
Providers “should counsel all gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW) with a history of at least one bacterial sexually transmitted infection” in the past 12 months, the CDC’s 2024 recommendation says, and offer doxyPEP through shared decision-making. That’s its strongest call. In shared decision-making, you and your provider weigh the benefits and harms together.
The guidelines reach past that group in two directions:
- MSM and trans women without a recent STI. DoxyPEP “could be discussed” with people who haven’t had an STI in the past year but whose sex puts them at higher risk. The trials didn’t test that group directly.
- Everyone else. “No recommendation can be given at this time on the use of doxy PEP for cisgender women, cisgender heterosexual men, transgender men, and other queer and nonbinary persons,” the CDC says. Providers can use clinical judgment.
Clinical data for those groups “are limited,” according to the CDC. The gap tracks who has been studied. It’s no verdict on anyone’s sex life.
The World Health Organization followed in 2026. “Doxycycline PEP may be offered to men who have sex with men and transgender women for the prevention of bacterial STIs,” its July 14, 2026 guideline says. The WHO rated it a conditional recommendation with moderate-certainty evidence. “This new WHO recommendation marks an important step forward in expanding STI prevention options,” Dr. Tereza Kasaeva, director of WHO’s Department for HIV, TB, Hepatitis and STIs, said in the May 28, 2026 announcement.
DoxyPEP Trial Results, From San Francisco to Kenya
Four randomized trials shaped the guidance. The three in MSM and trans women worked. The one in cisgender women didn’t.
| Trial | Who enrolled | Result |
|---|---|---|
| DoxyPEP (San Francisco and Seattle, NEJM, April 2023) | 501 MSM and trans women on PrEP or living with HIV, with an STI in the past year | STIs found at 10.7% of quarterly visits on doxyPEP vs. 31.9% on standard care in the PrEP group |
| IPERGAY substudy (France, Lancet Infectious Diseases, 2018) | 232 HIV-negative MSM and trans women on PrEP | Chlamydia down 70%, syphilis down 73%, no significant change in gonorrhea, per the CDC |
| DOXYVAC (Paris, Lancet Infectious Diseases, 2024) | 545 MSM on PrEP with an STI in the past year | 83% lower risk of a first chlamydia or syphilis infection (adjusted hazard ratio 0.17) |
| dPEP Kenya (NEJM, December 2023) | 449 cisgender women ages 18 to 30 on HIV PrEP | No significant reduction in STIs (relative risk 0.88) |
In the DoxyPEP trial’s PrEP group, the relative risk was 0.12 for chlamydia, 0.13 for early syphilis and 0.45 for gonorrhea. The CDC ran the math: about five people needed to use doxyPEP to prevent one quarterly checkup with a new STI (4.7 among PrEP users, 5.3 among people living with HIV). The trial’s final results came out in 2025 and held up, with STIs in 12.0% of quarters on doxyPEP vs. 30.5% on standard care.
DOXYVAC’s final analysis showed a 33% lower gonorrhea risk, its sponsor, the French agency ANRS, later reported.
Why DoxyPEP Didn’t Work in the Kenya Trial
“According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low,” the dPEP Kenya researchers wrote. That trial is why the CDC stops short of recommending doxyPEP for cis women. Women in the doxyPEP group reported covering their sex with a dose in 78% of weekly surveys, the CDC noted. Their hair told a different story. Doxycycline turned up in only 58 of 200 hair samples (29.0%). Low adherence might explain the result, the CDC says, and “biologic differences” still need study. Every gonorrhea sample tested in that trial was resistant to doxycycline.
What DoxyPEP Prevents and What It Doesn’t
| Infection | Does doxyPEP help? |
|---|---|
| Syphilis | Yes, strong protection in trials |
| Chlamydia | Yes, strong protection in trials |
| Gonorrhea | Partly, and protection depends on local resistance |
| HIV | No. Use PrEP, condoms or both |
| Herpes, HPV, hepatitis | No |
| Mpox | No. The JYNNEOS vaccine is the prevention tool |
Gonorrhea is the weak link. Doxycycline isn’t a recommended gonorrhea treatment “because of elevated antimicrobial resistance,” the CDC notes, though it “remains effective against many strains.” Gayety’s PrEP guide compares pills and shots for HIV. Mpox is still circulating, with clade I cases in California this fall.
DoxyPEP Resistance: Gonorrhea and Staph Data From 2025 and 2026
In 2024 the CDC called long-term harms “unknown but potentially concerning” and said resistance “will need to be monitored.” Studies from the first big rollouts are now in.
Gonorrhea resistance climbed fast. In King County, Washington, the share of gonorrhea samples from MSM with tetracycline resistance hovered around 27% from 2017 through early 2023. By mid-2024 it hit 70%, according to a 2025 Clinical Infectious Diseases study. High-level resistance went from 2% in early 2021 to 65%. That climb began before King County issued doxyPEP guidelines in the spring of 2023. Taking more than three doses a month was linked to resistant gonorrhea. Any use, on its own, was not.
Gonorrhea protection faded in Southern California. A Kaiser Permanente study of 26,582 people, published in 2026 in The Lancet Infectious Diseases, put doxyPEP at 66.5% effective against chlamydia and 60.7% against syphilis. Gonorrhea went the other way. Effectiveness fell from 42.3% before statewide rollout to no measurable protection in the first half of 2025 (an estimate of minus 15%), as a resistance gene called tetM spread. The authors wrote that “protection against gonorrhoea might not be durable.”
Staph and strep shifted. Overall staph carriage in the nose fell in the original trial. But the share of tested participants carrying tetracycline-resistant staph rose from 5% to 13%, the CDC reported. In King County, the study found tetracycline-resistant staph colonization in 18% of doxyPEP users vs. 8% of nonusers, plus more group A strep among users. Those swabs measured carriage. They didn’t measure illness.
Syphilis and chlamydia are holding. The WHO says no resistance in chlamydia or syphilis has been shown. In a 2025 lab study, repeated low-level doxycycline exposure did not produce resistance in the syphilis bacterium.
King County’s syphilis diagnoses ran about 52% below the projected trend after local doxyPEP implementation began in March 2023, according to an interrupted time series analysis published in 2026. Cases fell among cisgender women too, a group that rarely gets doxyPEP. Syphilis in pregnant people and congenital syphilis still rose. A design like that shows a drop lining up with the rollout. It can’t prove doxyPEP caused all of it.
“As additional data are available, CDC will update these guidelines,” the agency’s provider page says. As of Nov. 13, 2026, the CDC hadn’t revised its 2024 recommendation.
DoxyPEP Side Effects and Safety Tips
Most people tolerate doxycycline well. The CDC lists sun sensitivity, irritation of the esophagus and stomach upset, including nausea, vomiting and diarrhea. Stomach side effects were more common on doxyPEP in the IPERGAY substudy (53% vs. 41%). In DOXYVAC, 2% stopped because of stomach problems, and one person had a serious drug-related skin reaction (a fixed-drug eruption).
The DoxyPEP trial attributed five grade 3 adverse events to doxycycline and no serious ones. “No clinically relevant interactions between doxycycline and gender-affirming hormonal therapy are likely,” the CDC says of trans women. Doxycycline does interact with other drugs. Give your provider your full medication list, over-the-counter products included.
How to Get DoxyPEP and What Follow-Up Looks Like
You’ll need a prescription. Ask a primary care provider, an LGBTQ+ health center, a sexual health clinic or a telehealth service that offers it. The CDC tells providers to prescribe enough doses to last until your next visit, based on how often you have sex. Before you go, ask what the prescription, testing and visits will cost.
Testing comes with it. The CDC recommends gonorrhea and chlamydia tests at every body site exposed during sex, plus a syphilis blood test at the start and every 3 to 6 months. Your provider should recheck whether you still need doxyPEP on that same schedule. If you’re HIV-negative, keep up HIV testing on your usual schedule. People living with HIV should stay connected to care.
The CDC’s Get Tested locator lists HIV and STI testing sites near you, including free or low-cost clinics. One line that works at the appointment: “I had syphilis, chlamydia or gonorrhea in the past year, and I’d like to talk about doxyPEP.”
DoxyPEP FAQ
How effective is doxyPEP?
Per the CDC, trials in MSM and trans women showed it reduced syphilis and chlamydia by more than 70% and gonorrhea by about 50%. Where resistant strains are common, recent real-world data show gonorrhea protection dropping.
How soon after sex do you take doxyPEP?
As soon as possible, and within 72 hours. The WHO says ideally within 24 hours.
Can you take doxyPEP every day?
You take it after sex, not on a daily schedule, and never more than 200 mg in 24 hours. In the King County study, heavier use was linked to resistant gonorrhea.
Does doxyPEP prevent HIV?
No. It works only against bacteria. For HIV, use PrEP, condoms or both.
Can women take doxyPEP?
The CDC makes no recommendation for cisgender women. The one trial in that group, in Kenya, didn’t show a benefit. Providers can still discuss it case by case.
Does doxyPEP work against gonorrhea?
Less reliably than against syphilis and chlamydia. In a 2026 Southern California study, its gonorrhea protection fell to near zero as resistance spread.
Does doxyPEP cause antibiotic resistance?
Studies link it to more tetracycline-resistant gonorrhea and staph. How much doxyPEP itself drives that is still debated. No resistance has been shown in syphilis or chlamydia.
Do you need a prescription for doxyPEP?
Yes. Doxycycline is prescription-only in the U.S. Health centers, sexual health clinics and some telehealth services prescribe it.
