Sibling and twin study designs provide control for confounding factors that are typically unmeasured in traditional cohort studies. Using nationally representative data from the National Longitudinal Study of Adolescent Health collected at 3 visits during 1994-2002, the authors evaluated the longitudinal association between birth weight and later obesity in a traditional cohort study (n = 13,763; ages 11-21 years at baseline), controlling for sex, age, race/ethnicity, and parental education. Among persons with a nonobese mother, high birth weight (>4 kg) participants were more likely than normal birth weight (>/=2.5-</=4 kg) participants to become obese later in life (incidence rate ratio = 1.46, 95% confidence interval: 1.28, 1.67). In a matched sibling pair sample (full siblings: n = 513; monozygotic twins: n = 207; dizygotic twins: n = 189), the authors examined longitudinal within-pair differences. Birth weight difference was positively associated with body mass index difference later in life for female monozygotic pairs only (beta = 2.67, 95% confidence interval: 0.99, 4.35). Given the null associations observed in the sibling sample, the commonly observed positive association between birth weight and later obesity from cohort analyses may be attributed to confounding by maternal characteristics. Further research is needed to identify specific factors that contribute to the birth weight-obesity relation.