No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.