BACKGROUND: The success of antiretroviral therapy (ART) has led to dramatic changes in causes of morbidity and mortality in HIV-infected individuals. As chronic diseases rates have increased in HIV+ populations, modifiable risk factors such as obesity have increased in importance. Our objective was to evaluate factors associated with weight change among patients receiving ART. METHODS: ART-naïve patients initiating therapy at the University of Alabama - Birmingham 1917 HIV/AIDS Clinic from 2000- 2008 were included. Body Mass Index (BMI) was categorized as: underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9) and obese (≥30). Linear regression models were used to evaluate overall change in BMI and factors associated with increased BMI category 24 months following ART initiation. RESULTS: Among 681 patients, the mean baseline BMI was 25.4 ± 6.1; 44% of patients were overweight/obese. At 24 months, 20% of patients moved from normal to overweight/obese or overweight to obese BMI categories. Greater increases in BMI were observed in patients with baseline CD4 count < 50 cells/µl (3.4 ± 4.1, P<0.01) and boosted protease inhibitor use (2.5±4.1 P=0.01), but did not account for all of the variation observed in weight change. CONCLUSIONS: The findings that almost half of patients were overweight or obese at ART initiation, and 1 in 5 patients moved to a deleterious BMI category within 2 years of ART initiation are alarming. ART therapy provides only a modest contribution to weight gain in patients. Obesity represents a highly prevalent condition in patients with HIV infection and an important target for intervention.