OBJECTIVE We surveyed men who have sex with men (MSM) to determine whether sexual risk behaviors, recent drug use, and other psychosocial problems differed between men who engaged in one-on-one and group sexual encounters. METHODS We conducted an Internet-based cross-sectional survey of 7158 MSM aged 18 years or older in the United States recruited from a gay-oriented sexual networking Web site in 2008. Among MSM who engaged in group sexual encounters, we compared their past-60-day sexual behaviors in one-on-one encounters and group sexual encounters. We also compared risk profiles and syndemic production between men who did and did not participate in group sex. RESULTS Men reporting a group-sex encounter had significantly higher polydrug use and sexual risk than did the men not reporting group sex in the past 60 days. The odds of engaging in group sex with 4 or more sexual partners significantly increased with the number of psychosocial problems, supporting evidence of syndemic production. CONCLUSIONS We identified a particularly high-risk subgroup in the MSM population with considerable psychosocial problems that may be reached online. Research is needed on how to engage these high-risk men in combination prevention interventions.