We evaluated factors associated with low birth weight (LBW) in an HIV-infected cohort (n = 772) and a general sample (n = 2,377) of women delivering a live singleton in federal fiscal years 1989 and 1990 while enrolled in New York State Medicaid. The association of LBW and HIV infection was studied in logistic models, controlling for illicit drug use, demographic characteristics, adequacy of prenatal care, and medical risk factors. Overall, 29% of the HIV-infected women had a LBW infant, compared to 9.3% of the general sample (p < 0.001). The adjusted odds of LBW for HIV-infected women were twofold higher than for uninfected women [odds ratio (OR) = 2.04 and 95% confidence interval (CI) = 1.54, 2.69]. Odds of LBW were also increased for illicit drug users (OR = 2.16; 95% CI = 1.59, 2.94), cigarette smokers (OR = 1.81; 95% CI = 1.37, 2.39), and African-American versus non-Hispanic white women (OR = 1.89; 95% CI = 1.31, 2.72). Lower odds appeared for women with adequate prenatal care (OR = 0.54; 95% CI = 0.42, 0.68). Among only women with full-term deliveries, the association of HIV with LBW remained strong as we found nearly threefold greater odds of LBW for HIV-infected women. This study indicates that HIV-infected women have an increased risk of bearing a LBW infant, even after adjusting for the effects of drug use, health care delivery, and other social and medical risk factors.