The Soweto Men's Study assessed HIV prevalence and associated risk factors among MSM in Soweto, South Africa. Using respondent driven sampling (RDS) recruitment methods, we recruited 378 MSM (including 15 seeds) over 30 weeks in 2008. All results were adjusted for RDS sampling design. Overall HIV prevalence was estimated at 13.2% (95% confidence interval 12.4-13.9%), with 33.9% among gay-identified men, 6.4% among bisexual-identified men, and 10.1% among straight-identified MSM. In multivariable analysis, HIV infection was associated with being older than 25 (adjusted odds ratio (AOR) 3.8, 95% CI 3.2-4.6), gay self-identification (AOR 2.3, 95% CI 1.8-3.0), monthly income less than ZAR500 (AOR 1.4, 95% CI 1.2-1.7), purchasing alcohol or drugs in exchange for sex with another man (AOR 3.9, 95% CI 3.2-4.7), reporting any URAI (AOR 4.4, 95% CI 3.5-5.7), reporting between six and nine partners in the prior 6 months (AOR 5.7, 95% CI 4.0-8.2), circumcision, (AOR 0.2, 95% CI 0.1-0.2), a regular female partner (AOR 0.2, 95% CI 0.2-0.3), smoking marijuana in the last 6 months (AOR 0.6, 95% CI 0.5-0.8), unprotected vaginal intercourse in the last 6 months (AOR 0.5, 95% CI 0.4-0.6), and STI symptoms in the last year (AOR 0.7, 95% CI 0.5-0.8). The results of the Soweto Men's Study confirm that MSM are at high risk for HIV infection, with gay men at highest risk. HIV prevention and treatment for MSM are urgently needed.