Emerging evidence suggests that fetal environmental exposures impact on future development of obesity. The objectives of this study were to assess the relationships between (i) maternal insulin sensitivity and glucose tolerance status in pregnancy and (ii) early infant weight gain and adiposity in the first year of life. In this prospective cohort study, 301 women underwent oral glucose tolerance testing for assessment of glucose tolerance status and insulin sensitivity (IS(OGTT)) in pregnancy. Their infants underwent anthropometric assessment at 12 months of age, including determination of weight gain in the first year of life and sum of skinfold thickness (SFT), a measure of infant adiposity. Infant weight gain and sum of SFT at 12 months did not differ according to maternal glucose tolerance status. On univariate analyses, weight gain from 0 to 12 months and sum of SFT were negatively associated with maternal IS(OGTT) during pregnancy. On multiple linear regression analysis, negative independent predictors of weight gain from 0 to 12 months were maternal IS(OGTT) during pregnancy (t = -2.73; P = 0.007), infant female gender (t = -3.16; P = 0.002), and parental education (t = -1.98; P = 0.05), whereas white ethnicity was a positive independent predictor (t = 2.68; P = 0.008). Maternal IS(OGTT) (t = -2.7; P = 0.008) and parental education (t = -2.58; P = 0.01) were independent negative predictors of sum of SFT at 12 months. Independent of maternal glucose tolerance status, maternal insulin resistance during pregnancy is associated with increased infant weight gain and adiposity over the first year of life. Further longitudinal study to evaluate obesity in this group of children will increase our understanding of the contribution of the intrauterine environment to their long-term health.