Objective: To compare the interpregnancy weight gain in women whose first infant had a major congenital anomaly vs. those without an affected child. Design: Nationwide cohort study Setting: Denmark Population: All primigravid women with two consecutive singleton births between January 2004 and December 2017. Main Outcome Measure: Inter-pregnancy weight difference Methods: Multivariable linear regression compared women whose infant had an anomaly vs. those whose infant did not, adjusting for interpregnancy time interval, demographics, smoking and health status at the first pregnancy. Results: Of the 199,536 women, 4035 (2.0%) had a child with an anomaly at the first birth. The mean (SD) maternal BMI at the start of the first pregnancy was 24.2 (4.9) and 23.8 (4.6) kg/m2 in women with, and without, an anomaly-affected newborn. By the start of the second pregnancy, their interpregnancy weight gain was 4.7% and 4.2%, respectively – an adjusted absolute higher gain of 0.34% (95% CI 0.11 to 0.58) or 0.13 kg (95% CI 0.01 to 0.26) in women with an anomaly-affected first-born infant. Compared to those with an unaffected pregnancy, the interpregnancy weight gain difference was greatest in women whose first-born infant had a multi-organ anomaly (0.73%, 95% CI -0.10 to 1.57). Weight gain was more pronounced in women whose infants spent >30 days in hospital between pregnancies. Conclusions: Mothers of an infant with a major congenital anomaly have higher weight gain after pregnancy. Strategies are needed to support a healthy lifestyle in these women.