Mounting evidence has linked postnatal antibiotic use with body mass index (BMI) in children, but the influence of prenatal antibiotic use on offspring obesity risk remains unclear. We aimed to assess the association between fetal exposure to antibiotics and obesity at ages 4 and 7 years among 43,332 children using a multicenter prospective cohort of the US Collaborative Perinatal Project (1959-1976). Antibiotic use was ascertained for mothers during pregnancy. Modified Poisson regression models were used to estimate risk ratios for obesity (BMI >95th percentile), and linear mixed models were applied to assess the association with BMI z score. Repeated prenatal exposure to antibiotics was associated with childhood obesity at age 7 years, and risk of obesity tended to increase with an increasing number of antibiotic exposures (for 2-3 exposures, risk ratio (RR) = 1.22, 95% confidence interval (CI): 1.04, 1.44; for ≥4 exposures, RR = 1.34, 95% CI: 1.03, 1.73). The magnitude of association was strongest for repeated exposures in the second trimester (RR = 1.40, 95% CI: 1.16, 1.71). Prenatal antibiotic use was not associated with obesity or BMI z score at age 4 years. These findings support an increased risk of mid-childhood obesity with repeated use of antibiotics during pregnancy.