BACKGROUND: Infant weight gain is positively related to adulthood body mass index (BMI), but it is unknown whether or not this association is stronger for individuals born during (compared with before) the obesity epidemic. OBJECTIVES: The aim of the study was to examine how the infant weight gain-adulthood BMI association might have changed across successive birth year cohorts spanning most of the 20th century. METHODS: The sample comprised 346 participants in the Fels Longitudinal Study. Confounder-adjusted regression models were used to test the associations of conditional weight-for-length Z-score, capturing weight change between ages 0-2 years, with young adulthood BMI and blood pressure, including cohort [1933-1949 {N = 137}, 1950-1969 {N = 108}, 1970-1997 {N = 101}] as an effect modifier. RESULTS: Conditional weight-for-length Z-score was positively related to adulthood BMI, but there was significant effect modification by birth year cohort such that the association was over two times stronger in the 1970-1997 cohort (β 2.31; 95% confidence interval 1.59, 3.03) compared with the 1933-1949 (0.98; 0.31, 1.65) and 1950-1969 (0.87; 0.21, 1.54) cohorts. A similar pattern was found for systolic blood pressure. CONCLUSIONS: The infant weight gain-adulthood BMI association was over two times stronger among a cohort born during the obesity epidemic era compared with cohorts born earlier in the 20th century.