This study analyzed data from a large prospective epidemiologic cohort study among men who have sex with men (MSM), the Multicenter AIDS Cohort Study, to assess syndemic relationships among black MSM in the cohort (N = 301). We hypothesized that multiple interconnections among psychosocial health conditions would be found among these men, defining syndemic conditions. Constituents of syndemic conditions measured included reported depression symptoms, sexual compulsiveness, substance use, intimate partner violence (IPV), and stress. We found significant evidence of syndemics among these black men: depression symptoms were independently associated with sexual compulsiveness (odds ratios [OR]: 1.88, 95% CI = 1.1, 3.3) and stress (OR: 2.67, 95% CI = 1.5, 4.7); sexual compulsiveness was independently associated with stress (OR: 2.04, 95% CI = 1.2, 3.5); substance misuse was independently associated with IPV (OR: 2.57, 95% CI = 1.4, 4.8); stress independently was associated with depression symptoms (OR: 2.67, 95% CI = 1.5, 4.7), sexual compulsiveness (OR: 2.04, 95% CI = 1.2, 3.5) and IPV (OR: 2.84, 95% CI = 1.6, 4.9). Moreover, men who reported higher numbers of syndemic constituents (three or more conditions) reportedly engaged in more unprotected anal intercourse compared to men who had two or fewer health conditions (OR: 3.46, 95% CI = 1.4-8.3). Findings support the concept of syndemics in black MSM and suggest that syndemic theory may help explain complexities that sustain HIV-related sexual transmission behaviors in this group.