Since the introduction of highly active antiretroviral therapy (HAART) and the subsequent increased life expectancy in HIV-infected persons, non-HIV-related diseases have become an important cause of morbidity and mortality. This cross-sectional study reports the prevalence of overweight and obesity, and sociodemographic, psychological, and substance use-related risk factors for elevated body mass index (BMI) among 2157 HIV-seropositive (HIV+) in comparison to 730 HIV-seronegative (HIV-) participants in the Women's Interagency HIV Study (WIHS). Separate univariable and multivariate linear regression analyses were completed for HIV+ and HIV- women. Our study revealed a similar proportion of obesity (body mass index [BMI] >or=30) among HIV+ (33%) and HIV- women (29%) (p = 0.12), as well as comparable median BMI (HIV+: 26.1 versus HIV-: 26.7, p = 0.16). HIV+ compared to HIV- women, respectively, were significantly (p < 0.01) older (median = 35.6 versus. 32.5), but similar (p = 0.97) by race/ethnicity (57% African American, 28% Hispanic, and 15% white for both). In multivariate models for both HIV+ and HIV- women, African American race/ethnicity was significantly (p < 0.05) associated with higher BMI, while higher quality of life score and illicit hard drug use were associated with lower BMI. Additionally, smoking, alcohol use, markers of advanced HIV infection (AIDS diagnosis, elevated HIV viral load, low CD4 count), and a history of antiretroviral therapy use (ART) were also associated with lower BMI among HIV+ women. In conclusion, risk factors for elevated BMI were similar for HIV+ and HIV- women in the WIHS. For HIV+ women, all markers of advanced HIV infection and ART use were additionally associated with lower BMI.