Aim: Current literature lacks clear recommendations for the clinical management of pregnancies in which fathers are exposed to methotrexate prior and during conception. This highlights the need to expand the evidence regarding the fetal safety of paternal methotrexate exposure. Objective of this meta-analysis was to explore whether there is an association between major congenital malformations and other adverse pregnancy outcomes following paternal methotrexate exposure through a systematic review and meta-analysis. Methods: PubMed, Web of Science, and Reprotox databases were searched through December 2023. Cohort and case-control studies with paternal exposure to methotrexate were included. Results: The primary outcome of interest was the major congenital malformations following paternal methotrexate exposure during preconception and at conception. Secondary outcomes were the occurrence of cardiac malformations, spontaneous abortion, live birth, elective terminations, stillbirth, and preterm birth. Among the outcomes, only major congenital malformations, stillbirth, and preterm birth were eligible for quantitative analysis. No significant increases in the risk of major congenital malformations (aOR 1.00; [%95CI 0.62, 1.61]) (I2=%0, P=0.81), stillbirth (OR 0.85; [95%CI 0.11, 6.45]) (I2=%0, P=0.65) or preterm birth(OR 0.95; [%95CI 0.59, 1.53]) (I2=%26, P=0.26) were observed following paternal methotrexate exposure. Conclusion: These findings indicate that paternal methotrexate exposure does not significantly increase the risk of major congenital malformations, stillbirth, preterm birth. In addition, it was not ssociated with consistent or repetitive pattern of malformations. These findings suggest reassurance following paternal methotrexate exposure.