Lipodystrophy is a common long-term complication of HIV infection that may lead to decreased quality of life and less adherence to antiretroviral therapy (ART). A complete understanding of the etiology of HIV-associated lipodystrophy has not yet been achieved, although factors related to the virus, per se, and use of ART appear to be related. Alcohol use is common among HIV-infected patients and has biological effects on fat distribution, yet alcohol's relationship to HIV-associated lipodystrophy has not been examined. The goal of this clinical study was to assess the effect of alcohol consumption on lipodystrophy in HIV-infected adults with alcohol problems. This was a prospective study (2001-2006) of 289 HIV-infected persons with alcohol problems. The primary outcome was self-reported lipodystrophy, which was assessed at one time point (median 29 months after enrollment). Alcohol use was assessed every 6 months and classified as: abstinent at all interviews; > or = 1 report of moderate drinking but no heavy drinking; 1 or 2 reports of heavy drinking; or > or = 3 reports of heavy drinking. Multivariable logistic regression models were fit to the data. Fifty-two percent (150/289) of subjects reported lipodystrophy. Alcohol consumption was: 34% abstinent at all interviews; 12% > or = 1 report of moderate drinking, but no heavy drinking; 34% 1-2 reports of heavy drinking; and 20% > or = 3 reports of heavy drinking. Although not statistically significant, subjects with alcohol use had a higher odds of lipodystrophy (adjusted odds ratios and 95% confidence interval: > or = 1 report of moderate drinking, 2.36 [0.89, 6.24]; 1-2 reports of heavy drinking, 1.34 [0.69, 2.60]; > or = 3 reports of heavy drinking, 2.07 [0.90, 4.73]). Alcohol use may increase the odds of developing HIV-associated lipodystrophy among subjects with alcohol problems. However, larger studies are needed to fully elucidate the role and impact of alcohol consumption on the development of this common long-term complication of HIV infection and its treatment.