This cohort observational study was undertaken to test the hypothesis that the incidence of injuries for girls participating in high school sports is greater than that for boys. From 1995 through 1997, players were included in our study if they were listed on the school’s varsity team roster for boys’ or girls’ basketball, boys’ or girls’ soccer, boys’ baseball, or girls’ softball. Injuries and opportunities for injury were recorded daily. Certified athletic trainers reported injury and exposure data. Based on 39,032 player-seasons and 8988 reported injuries, the injury rates per 100 players for softball (16.7) and for girls’ soccer (26.7) were higher than for baseball (13.2) and boys’ soccer (23.4). The knee injury rates per 100 players for girls’ basketball (4.5) and girls’ soccer (5.2) were higher than for their male counterparts. Major injuries occurred more often in girls’ basketball (12.4%) and soccer (12.1%) than in boys’ basketball (9.9%) and soccer (10.4%). Baseball players (12.5%) had more major injuries than softball players (7.8%). There was a higher number of surgeries, particularly knee and anterior cruciate ligament surgeries, for female basketball and soccer players than for boys or girls in other sports.