We sought to determine predictors of fetal growth restriction in maternal HIV disease. Pregnant HIV-positive women on antiretroviral therapy were monitored with serial viral load and CD4 counts. Individualized growth potential (GP) percentile was calculated for birth weight (BW). BW <10th GP percentile defined fetal growth restriction (FOR). Multiple medical and social factors, CD4 count, viral load, and antiretroviral therapy were tested for impact on fetal growth using chi-square and multiple regression analysis. Two hundred eleven women were studied CD4 count <200 in the first trimester was strongly associated with FOR (odds ratio 8.75, 95% confidence interval 2.88 to 26.52). Maternal age (p = 0.02) and smoking (p = 0.03) were independent cofactors for FGR (Nagelkerke r(2) = 0.33). No other factors demonstrated an independent effect. Severity of maternal HIV disease as indicated by the CD4 count, rather than placental exposure to viral load, predicts FGR. Smoking has an independent detrimental effect on fetal growth.