INTRODUCTION: Prepregnancy obesity is associated with increased morbidity and mortality for mother and offspring. The objective of our study is to estimate the effect of maternal prepregnancy weight on placental pathological lesions.. METHODS: Data used for this study were from the U.S. Collaborative Perinatal Project, a large prospective cohort study. It consisted of 54390 women giving a singleton birth from 1959 to 1966. More than 84% of women had both detailed placental pathological examinations and anthropometric measurements. Logistic regression models were used to test the associations between maternal prepregnancy body mass index (BMI) and placental pathological lesions adjusting for potential confounders. Spline smoothing was applied to describe the relation of prepregnancy BMI and placenta weight-to-birthweight ratio. RESULTS: The prepregnancy obese women (BMI ≥ 30 kg/m(2)) showed a higher rate of maternal origin vascular lesions, maternal origin villous lesions, fetal neutrophilic infiltration, and meconium of fetal membrane compared with the normal-weight women (18.5 ≤ BMI < 24.9). The odds ratios ranged from 1.18 to 1.97 after adjusting for potential confounders. These higher odds were consistent in prepregnancy obese women without obstetric complications. Furthermore, placenta weight-to-birthweight ratio, the proxy for placenta insufficiency, was positively associated with maternal prepregnancy BMI.. CONCLUSIONS: Our study provides evidence that prepregnancy obesity exerts its adverse in-utero influence on placental pathology. These influences may have impact on maternal and fetal health. With obesity rising steadily, these results appear to raise serious public health concerns of prepregnancy obesity.