The role of psychiatric and substance use disorders in HIV transmission has not been fully elucidated, particularly among those living with the virus. We compared sex and drug risk behaviors for 228 HIV+ patients in four diagnostic groups: (1) no diagnosis; (2) psychiatric only; (3) substance dependence only; and (4) co-morbid psychiatric and substance dependence. Significant group differences were observed for having multiple sex partners, condom use, and injection drug use (IDU), but not for sharing of injection equipment. Patients with co-morbid psychiatric and substance disorders reported multiple sex partners most frequently, while substance dependence contributed to irregular condom use and IDU. Analysis by substance use subgroup (no dependence, alcohol dependence only, drug dependence only, co-morbid alcohol, and drug dependence) showed that alcohol dependence contributed to having multiple sex partners, while alcohol and drug dependence both contributed to irregular condom use. Meanwhile, only drug dependence contributed to drug risk. HIV+ patients should be screened for psychopathology, with risk reduction interventions tailored to diagnostic group to achieve maximum effect.