Objective: This study examined cognitive, psychiatric, and personality factors associated with risk behavior in HIV+ men and women to help clinicians identify vulnerable individuals and inform more focused interventions. Method: Data were collected from an ethnically-diverse, community-based sample of HIV+ men (n = 228) and women (n = 48). Risk was defined as the number of drug-related (i.e., injection drug use, needle sharing) or sexual risk-taking behaviors (i.e., unprotected sex, sex in exchange for drugs or money) in the past year. Participants received a comprehensive neuropsychological (NP) evaluation and completed psychiatric and personality measures (i.e., Drug Abuse Screening Test [DAST], Millon Clinical Multiaxial Inventory-III [MCMI-III], Sensation-Seeking Scale-V [SSS-V], Beck Depression Inventory-II [BDI-II]). Results: Results showed that men engaged in significantly more risk behavior than women (p < .01). Among men, more risk behavior was associated with better NP T-scores in all domains except motor and higher scores on the DAST, MCMI-III (i.e., Depressive, Antisocial, Schizotypal, Anxiety Disorder, and Drug Dependence subscales), and SSS-V (i.e., experience seeking scores (all p's < .05)). Among women, more risk behavior was associated with higher BDI-II scores and lower learning T-scores (all p's < .05). Conclusion(s): Our results showed a distinct pattern of factors associated with risk behavior that differed between men and women. Among men, risk was predicted by drug abuse, personality disturbance, and experience-seeking tendencies, whereas among women, it was predicted by low mood and reduced learning. Our findings highlight the complex underpinnings of risky behavior in this population and suggest unique vulnerabilities among men and women, which should be examined further.