BACKGROUND: Men who have sex with men living with human immunodeficiency virus have a high risk of anal cancer. We estimate the likely benefit of human papillomavirus (HPV) vaccination among participants of the Anal Cancer Examination study. METHODS: Anal swabs were collected for the detection and genotyping of anal HPV DNA by linear array (Roche Diagnostics) in this 2-year multicenter prospective cohort. We calculated the proportion of men, stratified by age, without detectable vaccine type-specific DNA. RESULTS: Overall, 255 men, with a median age of 50 years (interquartile range, 44-56 years) contributed 488.9 person-years of follow-up. After 2 years of follow-up, 149 (58%; 95% confidence interval [CI], 52-65) had at least 1 high-risk HPV (HRHPV), and 71 (28%, 95% CI, 22-34) had HPV types 16/18 detected. Assuming that DNA-negative men would receive vaccine protection, vaccination at baseline could potentially prevent HRHPV infection in 10.2% of men (95% CI, 6.8-14.6, 26 of 255) 2 years later from incident HRHPV covered by the bivalent and quadrivalent vaccine, and 29.4% of men (95% CI, 23.9-35.4, 75/255) from incident HRHPV covered by the nonavalent vaccine. CONCLUSION: Though there is high prevalence of anal HPV in men who have sex with men living with human immunodeficiency virus, there was also a high incidence of HRHPV vaccine types in the 2-year follow-up, indicating potential for prevention if these men were not previously infected with HPV vaccine types and were vaccinated at their baseline visit.