Serosorting is commonly employed by MSM to reduce HIV risk. We hypothesize that MSM perceive serosorting to be effective, and that serosorting is predicted by resilience and inversely related to syndemic characteristics. Surveys included 504 substance-using MSM. Logistic regression models examined syndemic and resilience predictors of serosorting, separately by serostatus. For HIV-positive men, positive coping behaviors (P = 0.015) and coping self-efficacy (P = 0.014) predicted higher odds, and cognitive escape behaviors (P = 0.003) lower odds, of serosorting. For HIV-negative men, social engagement (P = 0.03) and coping self-efficacy (P = 0.01) predicted higher odds, and severe mental distress (P = 0.001), victimization history (P = 0.007) and cognitive escape behaviors (P = 0.006) lower odds, of serosorting. HIV-negative serosorters reported lower perceptions of risk for infection than non-serosorters (P less than 0.000). Although high risk HIV-negative men may perceive serosorting to be effective, their high rates of UAI and partner change render this an ineffective risk reduction approach. Relevant public health messages are urgently needed.