We assessed whether economic, legal, and social hardships were associated with human immunodeficiency virus (HIV) risk among a sample of Black men who have sex with men (MSM) and whether associations were moderated by city of residence. The study analyzed baseline and follow-up data from HIV Prevention Trials Network 061 (N = 1553). Binary logistic regression assessed associations between hardships and HIV risk indicators. Multivariate regressions were used to test if city of residence had a moderating effect for hardships and HIV risks. Adjusted analyses showed that Black MSM with recent job loss were more likely to engage in condomless insertive anal intercourse (adjusted odds ratios (AOR) = 1.37, 95 % CI 1.01-1.87) and that those with recent financial crisis were more likely to have had two or more male sexual partners in the past 6 months (AOR = 1.65; 95 % CI 1.18-2.29). Black MSM with recent convictions were more likely to have a sexually transmitted infection at 6 months (AOR = 3.97; 95 % CI 1.58-9.94), while those who were unstably housed were more likely to have a sexually transmitted infection at 12 months (AOR = 1.71; 95 %CI 1.02 = 2.86). There were no city of residence and hardship interaction effects on HIV risks. Hardships are important factors that influence HIV risk for Black MSM. Integrating strategies that address structural factors that influence HIV risk may enhance HIV prevention interventions implementation efforts.