A population-based case-control study investigated the association between maternal exposure to air pollutants, carbon monoxide, nitrogen dioxide, ozone, sulfur dioxide, and particulate matter <10 μm in aerodynamic diameter during weeks 3–8 of pregnancy and the risk of selected cardiac birth defects and oral clefts in livebirths and fetal deaths between 1997 and 2000 in seven Texas counties. Controls were frequency matched to cases on year of birth, vital status, and maternal county of residence at delivery. Stationary monitoring data were used to estimate air pollution exposure. Logistic regression models adjusted for covariates available in the vital record. When the highest quartile of exposure was compared with the lowest, the authors observed positive associations between carbon monoxide and tetralogy of Fallot (odds ratio = 2.04, 95% confidence interval: 1.26, 3.29), particulate matter <10 μm in aerodynamic diameter and isolated atrial septal defects (odds ratio = 2.27, 95% confidence interval: 1.43, 3.60), and sulfur dioxide and isolated ventricular septal defects (odds ratio = 2.16, 95% confidence interval: 1.51, 3.09). There were inverse associations between carbon monoxide and isolated atrial septal defects and between ozone and isolated ventricular septal defects. Evidence that air pollution exposure influences the risk of oral clefts was limited. Suggestive results support a previously reported finding of an association between ozone exposure and pulmonary artery and valve defects.