Objective: To investigate the association between maternal body mass index (BMI) and major, structural congenital anomalies. Design: Cohort study using prospectively collected data. Methods: Data on all singleton pregnancies booked at five maternity units in the north of England between 01 January 2003 and 31 December 2005 and data on congenital anomalies notified to the Northern Congenital Abnormality Survey were linked using key variables. Maternal pre-gestational diabetic status was derived from the Northern Diabetes in Pregnancy Survey. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated by maximum-likelihood logistic regression models, with missing values modelled as explicit categories.Results: There was a total of 41 013 singleton pregnancies during the study period, of which 682 were affected by a structural congenital anomaly, a total prevalence of 166 (95% CI: 154, 179) per 10 000 registered births. Overall, the risk of a congenital anomaly was significantly increased among the maternal underweight (BMIp18.5 kg m -2 ; aOR ¼ 1.60, 95% CI: 1.09, 2.36; P ¼ 0.02) and maternal obese groups (BMIX30 kg m -2 ; aOR ¼ 1.30, 95% CI: 1.03, 1.63; P ¼ 0.03), but not for maternal overweight (BMI ¼ 25-29.9 kg m -2 ; aOR ¼ 0.85, 95% CI: 0.68, 1.06; P ¼ 0.15), compared with mothers of recommended BMI. Maternal obesity was associated with significantly increased risk of ventricular septal defect (aOR ¼ 1.56, 95% CI: 1.01, 2.40; P ¼ 0.04), cleft lip (aOR ¼ 3.71, 95% CI: 1.05, 13.10; P ¼ 0.04) and eye anomalies (aOR ¼ 11.36, 95% CI: 2.25, 57.28; P ¼ 0.003). Maternal underweight was associated with significantly increased risks of atrial septal defect (aOR ¼ 2.86, 95% CI: 1.18, 6.96; P ¼ 0.02), genital anomalies (aOR ¼ 6.30, 95% CI: 1.58, 25.08; P ¼ 0.009) and hypospadias (aOR ¼ 8.77, 95% CI: 1.42, 54.29; P ¼ 0.02). Conclusions: We found an overall increased risk of congenital anomalies in women who are obese and women who are underweight compared with women of recommended weight. Women should be made aware of these risks and supported to optimize their weight before pregnancy.