Approximately one third of all deliveries in the United States are via cesarean. Previous research indicates weight gain during pregnancy is associated with an increased risk of cesarean delivery. It remains unclear, however, whether and to what degree weight gain between deliveries (ie, interdelivery weight gain) is associated with cesarean delivery in a subsequent pregnancy following a vaginal delivery. The objective of the study was to determine whether interdelivery weight gain is associated with an increased risk of intrapartum cesarean delivery following a vaginal delivery. This was a case-control study of women who had 2 consecutive singleton births of at least 36 weeks' gestation between 2005 and 2016, with a vaginal delivery in the index pregnancy. Women were excluded if they had a contraindication to a trial of labor (eg, fetal malpresentation or placenta previa) in the subsequent pregnancy. Maternal characteristics and delivery outcomes for both pregnancies were abstracted from the medical record. Maternal weight gain between deliveries was measured as the change in body mass index at delivery. Women who underwent a subsequent cesarean delivery were compared with those who had a repeat vaginal delivery using χ2 statistics for categorical variables and Student t tests or analysis of variance for continuous variables. Multivariable logistic regression was used to determine whether interdelivery weight gain remained independently associated with intrapartum cesarean delivery after adjusting for potential confounders. Of 10,396 women who met eligibility criteria and had complete data, 218 (2.1%) had a cesarean delivery in the subsequent pregnancy. Interdelivery weight gain was significantly associated with cesarean delivery and remained significant in multivariable analysis for women with a body mass index increase of at least 2 kg/m2 (adjusted odds ratio, 1.53, 95% confidence interval, 1.03-2.27 for a body mass index increase of 2 kg/m2 to <4 kg/m2; adjusted odds ratio, 1.99, 95% confidence interval, 1.19-3.34 for body mass index increase of 4 kg/m2 or more). Furthermore, women who gained 2 kg/m2 or more were significantly more likely to undergo cesarean delivery specifically for the indications of arrest of dilation or arrest of descent (adjusted odds ratio, 2.01, 95% confidence interval, 1.21-3.33 for body mass index increase of 2 to <4 kg/m2; adjusted odds ratio, 2.34, 95% confidence interval, 1.15-4.76 for body mass index increase of ≥4 kg/m2). Contrarily, women who lost ≥2 kg/m2 were less likely to undergo any cesarean delivery (adjusted odds ratio, 0.41, 95% confidence interval, 0.21-0.78) as well as less likely to undergo cesarean delivery for an arrest disorder (adjusted odds ratio, 0.29, 95% confidence interval, 0.10-0.82). Weight gain or loss was not significantly associated with a cesarean delivery for fetal indications. Among women with a prior vaginal delivery, interdelivery weight gain was independently associated with an increased risk of intrapartum cesarean delivery in a subsequent pregnancy.