To determine the incidence of lower-extremity injury among high school cross-country runners and to identify risk factors for injury, the authors prospectively monitored a cohort of 421 runners competing on 23 cross-country teams in 12 Seattle, Washington, high schools during the 1996 cross-country season. Collected were daily injury and athletic exposure (AE) reports, a baseline questionnaire on prior running and injury experience, anthropometric measurements, and coaches' training logs. The overall incidence rate of injury was 17.0/1,000 AEs. Girls had a significantly higher overall injury rate (19.6/1,000 AEs) than boys did (15.0/1,000 AEs) (incidence rate ratio = 1.3, 95% confidence interval: 1.0, 1.6). Compared with boys, girls had significantly higher rates of injuries resulting in >or=15 days of disability. For the overall sample and for girls, Cox regression revealed that a quadriceps angle of >or=20 degrees and an injury during summer running prior to the season were the most important predictors of injury. For boys, a quadriceps angle of >or=15 degrees and a history of multiple running injuries were most associated with injury. Results suggest that the incidence of lower-extremity injuries is high for cross-country runners, especially girls. Preseason screening to determine risk factors should be examined as a preventive approach for identifying high-risk runners.