Objective: To assess the association between incident stressful life events (e.g., sexual and physical assault; housing instability; and major financial, employment, and legal difficulties) and unprotected anal or vaginal sexual intercourse (unprotected sex) among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (PLWHA). Methods: We assessed incident stressful events and unprotected sex over 27 months in 611 participants in an eight-site, five-state study in the Southeast United States. Using mixed-effects logistic models and separately estimating between-person and within-person associations, we assessed the association of incident stressful events with unprotected sex with all partners, HIV-positive partners, and HIV-negative/serostatus-unknown partners. Results: Incident stressful events reported at one third or more of interviews included major illness, injury or accident (non-HIV-related); major illness of a family member/close friend; death of a family member/close friend; financial stresses; and relationship stresses. In multivariable models, each additional moderately stressful event an individual experienced at a given time point above his or her norm (within-person association) was associated with a 24% to 27% increased odds of unprotected sex for each partner type. Conclusions: Risk reduction among PLWHA remains a major focus of efforts to combat the HIV epidemic. Incident stressful events are exceedingly common in the lives of PLWHA and are associated with increased unprotected sex. Efforts to either prevent the occurrence of such events (e.g., financial or relationship counseling) or address their sequelae (e.g., coping skills or other behavioral counseling) may help reduce secondary HIV transmission. © 2010 by the American Psychosomatic Society.