The purpose of this study was to examine factors associated with nonadherence to highly active antiretroviral therapy (HAART) in patients seen in HIV clinics throughout nonurban Louisiana. A convenience sample of 273 patients from 8 areas in nonurban Louisiana were interviewed to obtain demographic, clinical and adherence information. Associations between demographic, clinical, and behavioral factors and nonadherence were examined. Ideally, non-adherence should not exceed 5% in patients for whom HAART was prescribed. Mean age was 38.6 years (range, 19-66), 29.3% were female, 60.1% were African American, 34.4% reported nonadherence to their HAART medication (defined as the subject's self-report of missing any doses of HAART medication in the prior week). In the prior month, participants reported the following behaviors: binge drinking (12.8%), problem drinking (12.8%), and illicit drug use (16.5%). Depression was found in 49.8% of the respondents. In logistic regression analysis, problem drinking odds ratio [OR] (95% confidence interval [CI]): 3.92 (1.69,9.09) was found to be associated with nonadherence. Demographic and behavioral factors such as illicit drug use and depression were not associated with nonadherence on multivariable analysis. Problem drinking was associated with lack of adherence to HAART over the past week. Interventions to treat problem drinking are needed and may improve adherence to medication for HIV-infected persons living in rural, town, and small-city areas.