Introduction: Erectile dysfunction (ED) is a common diagnosis in up to 50% of men with HIV and prescription of erectile dysfunction medication (EDM) has been variably associated with increased risk behaviors and acquisition of sexually transmitted infections (STIs). Aim: We measured the association of EDM prescription with bacterial STI testing, STI infection and sexual behavior among men engaged in HIV care. Methods: A retrospective cohort study was conducted among HIV-infected men in care at an urban HIV clinic in Birmingham, Alabama between 2008 and 2016. Paired data analysis was used to compare STI testing and behavioral outcomes during the 12-month period before and after EDM prescription. Main Outcome Measures: Our study outcomes were STI testing and infection rates for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC) and incident syphilis as well as risk behaviors before and after EDM prescription. Results: Of 2924 HIV-infected men engaged in care, 589 (20%) initiated EDM with a new prescription from a clinic provider during the study period. During the year after EDM prescription, all STI testing rates decreased: CT (OR = 0.76; 95% CI: 0.58 - 1.01; P =.06), GC (OR = 0.76; 95% CI: 0.58 - 1.01; P =.06), and syphilis (OR = 0.28; 95% CI: 0.20 - 0.38; P <.001). A total of 43 STIs were detected in this study (10 CT, 8 GC, and 25 syphilis) and 42/43 occurred among men who have sex with men (MSM). Sexual activity rates were high before and after EDM (87.6% vs 82.9%; P =.08), and consistent condom use was rare (6.6% in both time periods). After EDM prescription, the median number of sexual partners in the past 6 months decreased from 2 to 1 among MSM and was stable at 1 among men who have sex with women. Clinical Implication: Management of ED in HIV clinic provides an excellent opportunity to discuss risk reduction, safer sex practices, and the importance of routine STI screening to prevent HIV/STI transmission. Strength & Limitations: This study provides insight into a common but understudied clinical scenario-ED in men with HIV-in an urban clinic population that is representative of the Southeastern United States. Adherence for ED medication was not assessed and STI risk behaviors were self-reported. Conclusion: EDM prescription did not lead to any detectable change in risk behavior in this setting but bacterial STI was common among MSM who were tested. Heudebert JP, Tamhane A, Burkholder GA, Dionne-Odom J. Erectile Dysfunction Medication Prescription: STI and Risk Behavior in Men with HIV. J Sex Med 2019;16:691–700.