In India, men who have sex with men (MSM) remain hidden because anal intercourse was criminalized and marriage socially required. We characterize HIV/STI prevalence among MSM in Tamil Nadu. Eligible participants were recruited using respondent-driven sampling in eight cities (n = 721). Median age was 28, 34% were married and 40% self-identified as homosexual. Median number of male partners in the prior year was 15; 45% reported any unprotected anal intercourse (UAI). HIV, herpes simplex virus-2 (HSV-2), chronic hepatitis B virus (HBV) and syphilis prevalence were 9, 26, 2 and 8%, respectively; among married men, all were higher: 14, 32, 3 and 11% (p < 0.01 for HIV and HSV-2). Less education, HSV-2, more male partners, UAI and not having a main male partner were associated with HIV prevalence. The high STI and UAI prevalence may lead to a burgeoning HIV epidemic among MSM, reinforcing the need for focused preventive measures incorporating complex circumstances.