OBJECTIVE: To estimate the association between interpregnancy change in body mass index (BMI) and the risk of gestational diabetes mellitus (GDM) in a second pregnancy. METHODS: In a retrospective cohort analysis of 22,351 women, logistic regression models provided adjusted estimates of the risk of GDM in women gaining 3.0 or more 2.0-2.9, and 1.0-1.9 BMI units, or losing 1.0-2.0 and more than 2.0 units between pregnancies (one BMI unit corresponds to 5.9 pounds for the average height [5 feet 4 inches] of the study population). Women with stable BMIs (+/-1.0 BMI unit) comprised the reference. RESULTS: For those with GDM in the first pregnancy, the age-adjusted risk of GDM in the second pregnancy was 38.19% (95% confidence interval [CI] 34.96-41.42); for those whose first pregnancy was not complicated by GDM, the risk was 3.52% (95% CI 3.27-3.76). Compared with women who remained stable, interpregnancy BMI gains were associated with an increased risk of GDM in the second pregnancy (odds ratio [OR] 1.71 [95% CI 1.42-2.07] for gaining 1.0-1.9 BMI units; OR 2.46 [95% CI 2.00-3.02] for 2.0-2.9 BMI units; and OR 3.40 [95% CI 2.81-4.12] for 3.0 or more BMI units). The loss of BMI units was associated with a lower risk of GDM only among women who were overweight or obese in the first pregnancy (OR 0.26 [95% CI 0.14-0.47] for the loss of at least 2.0 BMI units). In overweight and obese women, those with GDM in the first pregnancy that did not develop the condition again gained fewer BMI units than those experiencing recurrent GDM (mean change 0.66 [95% CI 0.25-1.07] compared with 2.00 [95% CI 1.56-2.43] BMI units, respectively). CONCLUSION: Interpregnancy increases in BMI between the first and second pregnancy increases a woman’s risk of GDM pregnancy.