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To examine male-female differences in pediatric overuse sports injuries.Cross-sectional epidemiological study.Tertiary level sports medicine division in a large academic pediatric medical center.Five percent probability sample of patients 5 to 17 years seen from January 1, 2000 to December 31, 2009. About 3813 charts reviewed. Final study cohort included 1614 patients.Nonlinear decomposition analysis of male-female differences in overuse injuries.Age, body mass index, history of previous injury, and activity type (contact/collision, team vs individual, “high overuse”).Females sustained approximately half of the total injuries. Fifty-two percent of the injuries were overuse, 61% to the lower extremity. A high proportion of tennis players, swimmers, dancers, track athletes, runners, gymnasts, and cheerleaders were seen for overuse injuries. Females sustained more overuse injuries versus males (63% and 40%, respectively). Males playing team sports have a 5.3 times higher likelihood of being seen for an overuse injury compared with males not playing team sports (P < 0.01). High-overuse sport participation increased overuse injury odds by a factor of 10 for males versus 3.6 for females (P ≤ 0.01 for males and females). Forty-six percent of the male-female difference in overuse injuries could be attributed to sport/activity characteristics—contact/collision, team, and high overuse.A large proportion of the sex discrepancy in overuse injuries in this cohort was attributed to compositional differences in sports played. Future research is needed to investigate the independent effect of sex on risk for pediatric sports injuries.This study provides a unique analysis of male-female differences in pediatric sports injuries and is the first study to estimate the impact of the different characteristics (ie, collision, team, high overuse) of sports children play on overuse injuries sustained by young athletes. The findings will help guide future prevention efforts.