The aim of our study was to determine the baseline prevalence of anal squamous intraepithelial lesions (SIL) and associated risk factors in HIV‐infected men who have sex with men (MSM) in a Spanish ongoing multicenter cohort. CoRIS‐HPV started in 2007, nested in the Spanish AIDS Research Network Cohort (CoRIS). Anal liquid cytology testing was performed. High‐risk human papillomavirus (HR‐HPV) infection was determined, and positive samples were genotyped. We analyzed all subjects up to April 2011. Multivariate logistic regression analyses were performed. A total of 551 subjects with baseline anal liquid cytologies were analyzed; 37.0% negative for intraepithelial lesion, 9.0% atypical squamous cells of uncertain significance (ASCUS), 41.0% low‐grade SIL, 4.0% high‐grade SIL and 9.0% inadequate. Prevalence of anal SIL (excluding ASCUS) in valid samples (n = 450) was 54.7% (95% confidence interval CI = 49.9–59.3). Globally HR‐HPV prevalence was 81.7% (95% CI = 78.0–85.2). Multiple infections (≥2 HR‐HPV genotypes) were documented in 77.7% (95% CI = 73.1–82.0). The only risk factor associated with anal SIL was the number of HR‐HPV types; MSM with five or more HR‐HPV genotypes had an odds ratio (OR) of anal SIL seven times greater (OR = 7.4; 95% CI = 2.8–19.6) than those with one HR‐HPV genotype. No associations were found for age, educational level, smoking, geographical origin, CD4 T‐cell count, antiretroviral treatment or number of sexual partners. The prevalence of anal SIL in young HIV‐positive MSM is high, and the main risk factor is multiple infections with HR‐HPV types. What's new? Anal squamous intraepithelial lesions (SILs) have been implicated as a risk factor for anal cancer in HIV‐positive men who have sex with men (MSM), and now, as detailed in this report, it appears that their development is associated with high risk (HR) human papillomavirus (HPV) genotype burden. Analysis of patients enrolled in the Spanish AIDS Research Network Cohort (CoRIS) revealed a seven‐fold increase in SIL risk for HIV‐positive MSM who had five or more detectable HR‐HPV genotypes. The findings could influence the development of SIL screening programs.