Studies of 1st trimester exposure to ACE inhibitors and angiotensin receptor blockers examining teratogenicity have shown conflicting results. We systematically reviewed the literature and performed a meta-analysis evaluating the risk of major malformations. For the meta-analysis, we included studies comparing 1st trimester exposure to no exposure, or to exposure to other antihypertensives. Additionally, we conducted a qualitative analysis of studies that did not meet the inclusion criteria for the meta-analysis. A significant risk ratio was found when the exposed group was compared with healthy controls but not when compared with other antihypertensives. The qualitative analysis did not demonstrate a specific pattern of major malformations. Our results suggest that 1st trimester exposure to ACE inhibitors and angiotensin receptor blockers is not associated with an elevated risk of major malformations compared with other antihypertensives. A 1st trimester exposure to antihypertensives in general may be associated with an elevated risk of major malformations.