Limited research has captured the wide varieties of distinct, but interrelated, life stressors that young men who have sex with men (YMSM) experience as emerging adults. We examined the way recent experiences of a diverse set of stressors predict illicit drug use, alcohol misuse, and inconsistent condom use (i.e., unprotected anal intercourse) among an ethnically diverse cohort of YMSM (N = 526). Results indicated that stress related to financial and health concerns were associated with increased risk for substance use, while health concerns and partner-related stress were associated with sexual risk-taking. Additional analyses indicated drug use and alcohol misuse did not significantly mediate the impact that stressors have on sexual risk. Findings show that stressors from different life domains can have impact on different HIV-risk behavior. Results challenge the way diverse stressful life experiences are conceptualized for this population. (Contains 4 tables and 2 figures.)