Abstract (a) Although prostate cancer is projected to be one of the most frequently diagnosed cancers in HIV-infected men overall, little is known about its risk in the sub-group with well-controlled HIV-infection. (b) We performed a retrospective cohort study to determine age-adjusted incidence of prostate adenocarcinoma in HIV-positive male veterans utilizing Veterans Administration (VA) healthcare between 10/01/1999 and 12/31/2016. HIV infection and prostate adenocarcinoma diagnosis as well as related clinical, sociodemographic, and lifestyle risk factors were obtained using extant VA administrative healthcare databases, the VA cancer registry, and augmented prostate cancer diagnosis with direct electronic medical record (EMR) review. We defined well controlled HIV as >60% of time with an undetectable HIV viral load and limited our analyses to those with a minimum of 90 days between HIV and prostate diagnosis, death, their last recorded health care encounter, or study end. We employed time-varying Cox proportional hazard regression models and used backward elimination to identify risk factors associated with incident prostate adenocarcinoma; effects are reported as Hazard ratios (HR) and 95% confidence intervals (CI). (c) During an average 10.26 years of follow-up, we identified 587 incident prostate adenocarcinomas among our cohort of 19,079 HIV positive men with well-controlled infection (age-adjusted incidence rate [IR] = 83.31 per 100,000-person years, 95% CI: 76.83-90.33); with a significant increasing trend over time. We identified several factors associated with significant increased risk of incident prostate adenocarcinoma, after adjusting for HIV medication use, in our well-controlled HIV-positive cohort including substance abuse (HR=1.68, 95% CI: 1.27-2.24, p=0.0003), age at HIV diagnosis (HR=1.73, 95% CI: 1.25-2.39, p=0.0010), and black race (HR=2.07, 95% CI: 1.58-2.72, p<.0001). History of alcohol abuse (HR=0.54, 95% CI: 0.39-0.75, p=0.0002), longer time with well-controlled infection (HR=0.63, 95% CI: 0.59-0.67, p<.0001), and receiving integrase inhibitors (HR=0.64, 95% CI: 0.45-0.92, p=0.041) were associated with reduced risk. Several risk factors included in the multivariable model, such as PSA testing, testosterone levels, and maximum BMI, were not found to be significantly associated with or protective for prostate cancer. (d) Further research is needed to confirm our findings and to better identify sub-groups of well-controlled HIV-positive men at greatest increased prostate cancer risk. Citation Format: Kathryn E. Royse, Jose M. Garcia, Donna L. White, Jennifer R. Kramer, Yongquan Dong, Suchismita Raychaudhury, Peter A. Richardson, Christine Hartman, Elizabeth Y. Chiao. Prostate adenocarcinoma incidence and risk factors in Veterans with well controlled HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5044.