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Methods and findings: We used data from four United States general youth population cohort studies: the National Longitudinal Study of Youth 1979 (NLSY-79), the NLSY-79 Children and Young Adult, the NLSY 1997 (NLSY-97), and the Wisconsin Longitudinal Study (WLS); a total of 12,250 siblings from 5,602 households followed from adolescence up to age 62. We used random effects within-between (REWB) and residualized quantile regression (RQR) models to compare between- and within-family estimates of the association between adolescent cognitive ability and adult BMI (20 to 64 years). In REWB models, moving from the 25th to 75th percentile of adolescent cognitive ability was associated with −0.95 kg/m2 (95% CI = −1.21, −0.69) lower BMI between families. Adjusting for family socioeconomic position reduced the association to −0.61 kg/m2 (−0.90, −0.33). However, within families, the association was just −0.06 kg/m2 (−0.35, 0.23). This pattern of results was found across multiple specifications, including analyses conducted in separate cohorts, models examining age-differences in association, and in RQR models examining the association across the distribution of BMI. Limitations include the possibility that within-family estimates are biased due to measurement error of the exposure, confounding via non-shared factors, and carryover effects.