BACKGROUND: Alcohol consumption during pregnancy is known to be associated with certain birth defects, but the risk of other birth defects is less certain. The authors examined associations between maternal alcohol consumption during pregnancy and craniosynostosis, omphalocele, and gastroschisis among participants in the National Birth Defects Prevention Study, a large, multicenter case-control study. METHODS: A total of 6622 control infants and 1768 infants with birth defects delivered from 1997-2005 were included in the present analysis. Maternal alcohol consumption was assessed as any periconceptional consumption (1 month prepregnancy through the third pregnancy month), and by quantity-frequency, duration, and beverage type. Alcohol consumption throughout pregnancy was explored for craniosynostosis since the period of development may extend beyond the first trimester. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis. OR were adjusted for age, race/ethnicity, and state of residence at time of infant's birth. Gastroschisis OR were also adjusted for periconceptional smoking. RESULTS: Periconceptional alcohol consumption and craniosynostosis showed little evidence of an association (OR 5 0.92; CI: 0.78-1.08), but alcohol consumption in the second (OR 5 0.65; CI: 0.47-0.92) and third trimesters (OR 5 0.68; CI: 0.49-0.95) was inversely associated with craniosynostosis. Periconceptional alcohol consumption was associated with omphalocele (OR 5 1.50; CI: 1.15-1.96) and gastroschisis (OR 5 1.40; CI: 1.17-1.67). CONCLUSIONS: Results suggest that maternal periconceptional alcohol consumption is associated with omphalocele and gastroschisis, and second and third trimester alcohol consumption are inversely associated with craniosynostosis. Birth Defects Research (Part A) 91: 623-630, 2011.