Background: Congenital heart defects (CHDs) are significant drivers of mortality and morbidity in children, folic acid supplementation for the pregnant month during or before delivery is said to influence risk reduction of congenital heart defects (CHDs). However, there are controversial claims and the hypothesis is concluded from limited epidemiologic studies. Aim of the Study: Conduct a systematic review and meta-analysis of published studies to reliably evaluate the correlation between Folic acid or multivitamins containing FA supplementation taken during pregnancy and the risk of CHDs. Methods: A systematic review and meta-analysis was conducted. PUBMED and EMBASE were searched to identify prospective cohort and case-control studies that had reported on the association between 1960 and 2017.Studies conducted in primarily high-risk populations (Case control and cohort studies) while participants in randomized controlled trials were excluded. Results: The search yielded 10 studies published between 2000 and 2013 enrolling 13126 female participants. These studies included only one cohort study, and nine case-control studies. The overall results of this meta-analysis provide evidence that maternal folate supplementation is associated with a significantly decreased risk of CHDs (RR = 0.69, 95% CI: 0.54–0.84). Statistically significant heterogeneity was detected (Q = 79.43, P < 0.001, I2 = 70.2%). Conclusion: FA supplementation during pregnancy significantly decreases the risk of CHDs in newborns.