Alcohol and drug use are common among HIV-infected patients and are important determinants of secondary transmission risk and medication adherence. As part of the Coping with HIV/AIDS in the Southeast (CHASE) Study, 611 HIV-infected patients were consecutively recruited from eight clinical care sites in five southeastern U.S. states in 2001-2002. We examined the distribution and predictors of alcohol and drug use in this sample with an emphasis on psychosocial predictors of use. In the prior 9 months, 27% of participants drank alcohol and 7% drank to intoxication at least weekly. The most common drugs used at least weekly were marijuana (12%) and crack (5%); 11% used a non-marijuana drug. 7% reported polysubstance use (use of multiple substances at one time) at least weekly. Injection drug use was rare (2% injected at least once in the past 9 months). There were few differences in alcohol and drug use across sociodemographic characteristics. Stronger adaptive coping strategies were the most consistent predictor of less frequent alcohol and drug use, in particular coping through action and coping through relying on religion. Stronger maladaptive coping strategies predicted greater frequency of drinking to intoxication but not other measures of alcohol and drug use. Those with more lifetime traumatic experiences also reported higher substance use. Interventions that teach adaptive coping strategies may be effective in reducing alcohol and substance use among HIV-positive persons. © 2008 Mary Ann Liebert, Inc.