Nitrogen oxide (NO x ) is produced during combustion at high temperature, which is a major constituent of air pollutants. Recent studies suggested inconsistent results on the association between NO x exposure and cardiovascular-related malformations. We aimed to assess aforementioned association in pregnant women in the first trimester and cardiovascular-related malformations of infants. A systematic literature review identified studies for observational studies about NO x exposure and cardiovascular-related malformation in PubMed. Random-effect models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned association. Finally, nine studies met the inclusion criteria. Overall, the SOR of cardiovascular-related malformation per 10 ppb increment in NO x and NO2 concentration was 1.01 (95% CI: 0.98-1.04; I2 = 38.6%, P = 0.09) and 0.99 (95% CI: 0.95-1.04; I2 = 37.8%, P = 0.13), respectively. Stratifying by study design, geographic locations, and confounded adjustments, the majority of strata showed negative results, which were consistent with the main findings. However, we found that exposure to NO x and NO2 in the first trimester increased the risk of coarctation of the aorta (COA) malformation by 13% and 19%, respectively. Our study provided limited evidence regarding the association between NO x exposure in the first trimester and cardiovascular-related malformations in infants.