Background: This study aimed to explore the developmental effects of prenatal exposure to Pb and Cd on infant cognitive development at 6 months of age. Methods: Between 2006 and 2010, the blood levels of Pb and Cd were measured in 884 mothers during their early and late pregnancy. The mental (MDI) and psychomotor (PDI) development index scores of the infants were assessed using the Bayley Scales of Infant Development. The development index scores were adjusted for birth weight, maternal age, maternal education level, family income, breastfeeding status, and residential area. Results: The geometric mean of the maternal blood concentration was 1.36 μg/dL (10th percentile = 0.83; 90th percentile = 2.13; range = 0.26-9.10) for Pb and 1.42 μg/L (10th percentile = 1.01; 90th percentile = 2.16; range = 0.03-9.87) for Cd during the early pregnancy period and 1.27 μg/dL (10th percentile = 0.77; 90th percentile = 2.10; range = 0.12-4.28) for Pb and 1.52 μg/L for Cd (10 percentile = 1.07; 90th percentile = 2.10; range = 0.43-3.73) during the late pregnancy period. The prenatal Pb and Cd concentrations during the early pregnancy period showed no association with the adjusted MDI or PDI scores. The antagonistic interaction between the prenatal Pb and Cd levels during the early pregnancy period had a significant effect on the MDI score (B= -4.64, 95% CI = -8.17 to -1.12, p= 0.01), but the effect of this interaction did not reach statistical significance for the PDI score (B= -3.69, 95% CI = -7.94 to 0.56, p= 0.09). The Pb levels during the late pregnancy period were inversely associated with the MDI score (B= -1.94, 95% CI = -3.60 to -0.29, p= 0.02) but not with the PDI score (B= -1.69, 95% CI = -3.65 to 0.27, p= 0.09). The prenatal Cd levels during the late pregnancy period showed no association with the MDI or PDI score. However, the MDI score (B= -3.20, 95% CI = -5.35 to -1.06, p< 0.01) and the PDI score (B= -2.86, 95% CI = -5.55 to -0.16, p= 0.04) of infants with Cd levels >1.51 μg/L were significantly associated with the Pb level, whereas there were no such associations for infants with Cd levels <1.51 μg/L. These results suggest that there is a synergistic effect modification between Pb and Cd during the late pregnancy period. Conclusions: These findings suggest that there is dose-dependent interaction between prenatal exposure to Pb and prenatal exposure to Cd. The results further demonstrate the biological complexities of examining the neurodevelopmental effects of co-exposure to multiple toxicants.