BACKGROUND: Substantial evidence suggests that weight gain in early life is associated with increased adiposity and other metabolic disorders later in life. It is, however, unknown whether physical activity (PA) may modify these associations. We aimed to examine whether objectively measured PA at 30 years modified the associations between conditional weight gain in infancy (0-2 y) and childhood (2-4 y) with fat mass index (FMI) and visceral abdominal fat measured at age 30 years. METHODS: Prospective birth cohort study in Pelotas, Brazil, including 1874 participants with weight data at birth, two and four years of age, and measures of FMI, visceral abdominal fat and PA at a mean age of 30.2 years. At age 30, time spent (min/day) in moderate-to-vigorous physical activity (MVPA) was measured objectively using a wrist-worn accelerometer worn for four to seven consecutive days.. Multiple linear regression analyses was performed to assess the associations between conditional weight gain and outcome variables at 30 years, adjusting for covariates. We examined whether PA modified the association between conditional weight gain and the outcomes of interest by introducing an interaction term (conditional weight gain × PA) in the models. RESULTS: Conditional weight gain in infancy and childhood were both positively associated with later FMI (infancy weight gain: β = 0.68, 95% CI: 0.48, 0.88; P < 0.001; childhood weight gain: β = 0.91, 95% CI: 0.70, 1.11; P < 0.001). A formal test for interaction suggested that MVPA at 30 years of age modified the association between childhood relative weight gain and later FMI (β = -0.006, 95% CI: -0.011, -0.001; P = 0.029), suggesting stronger associations between weight gain and FMI in those with lower levels of MVPA. Conditional weight gain in childhood was also positively associated with visceral abdominal fat (β = 0.24, 95% CI: 0.15, 0424, P < 0.001). There was no evidence for a modification of the latter association after adjustment for physical activity. CONCLUSION: Conditional weight gain between 2 and 4 years of age is associated with increased FMI at age 30 years. However, higher levels of MVPA appear to attenuate this detrimental association.