OBJECTIVE: To examine temporal changes in maternal weight and the association with major structural anomalies and other factors, such as diabetes, in our primary obstetric population. METHODS: We conducted a serial, cross-sectional study using a perinatal database to identify all women with singletons who delivered in our system from 1991 to 2004. Three 5-year time epochs were defined to compare patient cohorts. Maternal weight, body mass index (BMI), diabetes status, incidence of major anomalies, and demographic data were compared. Multiple logistic regression was performed to estimate factors contributing to anomaly rates. Results: A total of 41,902 pregnancies were included. In each time epoch, there was an increase in the mean maternal weight, the mean BMI, the proportion of women weighing in excess of 200 lb, the proportion with a BMI higher than 29, the prevalence of pregestational diabetes, and the prevalence of major anomalies (all P<.001). There was no significant independent association between maternal obesity and the presence of a major anomaly. In a multivariable logistic model, the major factor contributing to the increasing rate of congenital anomalies was the prevalence of pregestational diabetes (odds ratio 3.8, 95% confidence interval 2.1-6.6). The population-attributable risk of anomalies related to obesity increased from essentially 0% in 1991-1994 to 6.1% in 2000-2004, whereas that related to diabetes increased from 3.3% to 9.2% during the same time periods. Conclusion: Although the prevalence of maternal obesity and anomaly have increased, maternal weight alone was not associated with an increase in congenital anomalies. Instead, diabetes was significantly associated with the increase in the rate of anomalies seen in our population. Identification of maternal weight as a risk factor in epidemiologic studies may be a surrogate for pregestational diabetes. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.