Background: Congenital heart defects (CHDs) are the most prevalentheart disease in neonates. There is evidence suggesting that the risk ofCHDs may be related to maternal folate status as well as genetic variantsin folate-related genes. Aim of work: Investigating the relation betweenMTHFR C677T gene polymorphism and CHDs in full-term neonates&considering the possible role of folate supplementation in the preventionof CHDs. Methods: This prospective study included 26 cases and18 controls with their mothers. Detailed history was taken from eachmother through questionnaires. Echocardiography was done for allbabies. Neonates and mothers were subjected to DNA analysis forMTHFR C677T using polymerase chain reaction restricted fragmentlength polymorphism (PCR-RFLP). Results: we found an associationbetween either maternal or infant MTHFR C677T genotype with TGA&between infant MTHFR C677T genotype and each of ASD, VSD andPDA. Also, we found folic acid supplementation to be protective againstCHDs. Conclusion: MTHFR C677T polymorphism is associated withcertain subgroups of CHDs.