Context: The factors that govern skeletal responses to physical activity remain poorly understood. Objective: The aim of this study was to investigate whether gender or fat mass influences relationships between cortical bone and physical activity, after partitioning accelerometer outputs into low (0.5-2.1 g), medium (2.1-4.2 g), or high (>4.2 g) impacts, where g represents gravitational force. Design/Setting: We conducted a cross-sectional analysis in participants from the Avon Longitudinal Study of Parents and Children. Participants: We studied 675 adolescents (272 boys; mean age, 17.7 yr). Outcome Measures: We measured cortical bone parameters from peripheral quantitative computed tomography scans of the mid-tibia, adjusted for height, fat mass, and lean mass. Results: High-impact activity was positively associated with periosteal circumference (PC) in males but not females [coefficients (95% confidence intervals), 0.054 (0.007, 0.100) and 0.07 (-0.028, 0.041), respectively; showing sd change per doubling in activity]. There was also weak evidence that medium impacts were positively related to PC in males but not females (P = 0.03 for gender interaction). On stratifying by fat mass, the positive relationship between high-impact activity and PC was greatest in those with the highest fat mass [high impact vs. PC in males, 0.01 (-0.064, 0.085), 0.045 (-0.040, 0.131), 0.098 (0.012, 0.185), for lower, middle, and upper fat tertiles, respectively; high impact vs. PC in females, -0.041 (-0.101, 0.020), -0.028 (-0.077, 0.022), 0.082 (0.015, 0.148), P = 0.01 for fat mass interaction]. Similar findings were observed for strength parameters, cross-sectional moment of inertia, and strength-strain index. Conclusions: In late adolescence, associations between high-impact activity and PC are attenuated by female gender and low body fat, suggesting that the skeletal response to high-impact activity is particularly reduced in young women with low fat mass.