OBJECTIVE: To find out whether an association exists between obesity in non-diabetic African-American women and congenital malformations in their babies. METHODS: Using a retrospective study design in a large cohort of African American women, we identified deliveries in which children had birth defects. Because of its known association with congenital malformations, mothers with clinical diabetes, as well as certain other potential confounders, were excluded. Body mass indices (BMI = kg/m2) of women who delivered babies with birth defects (cases) were compared with randomly selected women who delivered babies without malformations (controls). Obesity was defined as BMI > or = 27. RESULTS: Among more than 38,000 deliveries, we found 130 cases of babies with birth defects. Of these, 63 babies had major congenital malformations and 67 had minor malformations. For purposes of comparison, we randomly selected 144 babies without birth defects to be controls. As compared to non-obese, non-diabetic African American women, obese non-diabetic African American women were significantly more likely to have babies with a cardiac anomaly (OR 6.5; 95% CI 1.2, 34.9; P = 0.025). Other organ-specific, major birth defects were not significantly associated with maternal obesity. CONCLUSIONS: In addition to urging reduction of excess weight prior to pregnancy, we need to ensure that all African American women with obesity have sophisticated mid-trimester ultrasound screening to look for major fetal cardiac malformations.