Several modifiable pre- and postnatal determinants of childhood overweight are known, but no one has examined how they influence risk of overweight in combination. We estimated the risk of overweight at age 3 years according to levels of maternal smoking during pregnancy, gestational weight gain, breastfeeding duration, and infant sleep duration. We studied 1,110 mother-child pairs in Project Viva, a prospective prebirth cohort study. The main outcome measure was child overweight (BMI for age and sex >or=95th percentile) at age 3. We ran logistic regression models with all four modifiable risk factors as well as the covariates maternal BMI and education, child race/ethnicity, and household income. From the model, we obtained the estimated probability of overweight for each of the 16 combinations of the four risk factors. During pregnancy, 9.8% of mothers smoked and 50% gained excessive weight. In infancy, 73% mother-child pairs breastfed for <12 m, and 31% of infants slept <12 h/day. Among the 3-year-old children in the cohort, 9.5% were overweight. In the prediction model, the estimated probability of overweight ranged from 0.06 among children exposed to favorable levels of all four risk factors, to 0.29 with adverse levels of all four. Healthful levels of four behaviors during early development predicted much lower probability of overweight at age 3 than adverse levels. Interventions to modify several factors during pregnancy and infancy could have substantial impact on prevention of childhood overweight.