We sought to determine whether genetic variants associated with diabetes and obesity predict gestational weight gain.A total of 960 participants in the Pregnancy, Infection, and Nutrition cohorts were genotyped for 27 single-nucleotide polymorphisms (SNPs) associated with diabetes and obesity.Among Caucasian and African American women (n = 960), KCNQ1 risk allele carriage was directly associated with weight gain (P < .01). In Bayesian hierarchical models among Caucasian women (n = 628), we found posterior odds ratios >3 for inclusion of TCF2 and THADA SNPs in our models. Among African American women (n = 332), we found associations between risk allele carriage and weight gain for the THADA and INSIG2 SNPs. In Bayesian variable selection models, we found an interaction between the TSPAN8 risk allele and pregravid obesity, with lower weight gain among obese risk allele carriers.We found evidence that diabetes and obesity risk alleles interact with maternal pregravid body mass index to predict gestational weight gain.