Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are known to cause fetal renal damage in pregnancy. Due to conflicting reports in the literature, their safety after first trimester exposure has been debated. Our aim was to determine whether the use of ACE inhibitors or ARBs in the first trimester of pregnancy is associated with an increased risk for major malformations or other adverse outcomes. All subjects were prospectively enrolled from among women contacting a teratogen information service. At initial contact, details of maternal medical history and exposures were collected and follow-up interviews were conducted to ascertain pregnancy outcomes. Two comparator groups, women with hypertension treated with other antihypertensives, and healthy controls were also recruited. Baseline maternal characteristics were not different among the three groups. There were no differences in rates of major malformations. Both the ACE-ARBs and disease-matched groups exhibited significantly lower birth weight and gestational ages than the healthy controls (P < 0.001 for both variables). There was a significantly higher rate of miscarriage noted in the ACE/ARB group (P < 0.001). These results suggest that ACE inhibitors/ARBs are not major human teratogens; however, they may be associated with an increased risk for miscarriage.