This research examines the levels of condom use self-efficacy in a population of men who have sex with men who are at great risk for contracting/transmitting HIV. It focuses on the relationship between condom use self-efficacy and risk involvement, and examines the factors associated with greater/lower levels of condom use self-efficacy. The data come from a national sample of men, randomly chosen, who used any of 16 websites specifically to identify other men with whom they could engage in unprotected sex. Data were collected between January 2008 and May 2009 from 332 men, via telephone interviews. Multivariate analyses and structural equation modeling were used to test a conceptual model based on syndemics theory. Overall levels of condom use self-efficacy were fairly high, and self-efficacy was related inversely to involvement in HIV risk practices. Six factors were found to be indicative of levels of condom use self-efficacy: the number of drug problems experienced, sexual role identity as a "bottom," not caring about the HIV serostatus of potential sex partners, experiencing childhood maltreatment, having confidence in HIV-related information provided in other men’s online profiles, and level of HIV knowledge. Condom use self-efficacy plays an integral role in HIV risk practices among high-risk men who have sex with men. This is true despite the fact that, overall, condom use self-efficacy levels were fairly high in this population.