OBJECTIVE To assess the period during infancy and childhood in which growth is most associated with adolescent adiposity and the metabolic syndrome (MS) and whether this differs depending on maternal smoking during pregnancy. STUDY DESIGN A longitudinal population-based cohort study among 772 girls and 708 boys. RESULTS Weight gains between ages 2-4 years and ages 4-7 years were most strongly associated with higher body mass index (BMI), sum of skinfold measurements, body fat percentage, and waist circumference at age 16. A one SD increase in weight between ages 2-4 and 4-7 years was associated with increases in outcome measures of +0.82 to +1.47 SDs (all P < .001), and with a less favorable MS score. In children whose mothers smoked during pregnancy, the association of relative weight gain during ages 2-4 years with adolescent BMI was stronger than in children whose mothers did not smoke. For adolescent BMI, the increase was 0.42 SD higher (P = .01). This was similar for the other adiposity measures. CONCLUSIONS Large relative increases in weight from ages 2 to 7 years are associated with adolescent adiposity and MS. This is more pronounced in adolescents whose mothers smoked during pregnancy.