Although it appears that some classes of antibiotics have been used relatively safely during pregnancy, there have not been large-scale studies that addressed safety or risk for many classes of antibacterial drugs. This study used data from the National Birth Defects Prevention Study to assess the risks of different classes of antibiotics taken during pregnancy. The study lends support to the established safety profiles for certain classes of antibacterials, like penicillins, erythromycins, and cephalosporins. However, several increased odds ratios were observed among women who took sulfonamides and nitrofurantoins. Sulfonamides were associated with an increased risk of anencephaly, hypoplastic left heart syndrome, coarctation of the aorta, transverse limb deficiency, and diaphragmatic hernia, while nitrofurantoins were associated with anophthalmos/microphthalmos, hypoplastic left heart syndrome, atrial septal defects, and cleft lip with cleft palate. These associations warrant further study because of the common use of these drugs.