In industrialized countries, prenatal exposure to maternal cigarette smoking (PEMCS) is the most common environmental insult to the fetus. Here, we tested the hypothesis that PEMCS amplifies accumulation of abdominal fat during the accelerated weight gain occurring in late puberty. This hypothesis was tested in 508 adolescents (12–18 years, 237 exposed prenatally to maternal cigarette smoking) in whom subcutaneous and intra-abdominal fat were quantified with magnetic resonance imaging (MRI). We found that, in early puberty, exposed and nonexposed adolescents did not differ in MRI-based measures of adiposity. In late puberty, on the other hand, exposed compared with nonexposed adolescents demonstrated markedly higher quantities of both subcutaneous fat (by 26%, P = 0.004) and intra-abdominal fat (by 33%, P = 0.001). These group differences remained virtually unchanged after adjusting for sex and potential confounders, including birth weight and breastfeeding. As such, our results suggest that PEMCS may represent a major risk factor for the development of abdominal obesity at the later stages of puberty.