Background: Medial tibial stres syndrome (MTSS) is a common injury among runners. Biomechanical factors, including navicular drop, have been suggested to increase the risk for MTSS. However, few researchers have examined this association, especially is adolescent runners. Thus, the purpose of this study was to determine if navicular drop is associated with the occurrence of MTSS in high school cross country runners. Methods: A prospecftive cohort of 105 high school runners was followed in eight Indiana high schools during the 2004 cross country season. Bilateral navicular drop and foot length were measured on each runner prior to the start of the season. Additional data collected included a baseline history form on previous running injury, running experience, orthotic use, height and weight. The runners were followed throughout the cross country season for occurrence of MTSS. Coaches and certified athletic trainers completed the Athletic Health Care System Daily Injury Report to document MTSS and other running-related injuries, time lost from injury, and athletic exposures (AEs) daily. The baseline history, navicular drop, and foot length measurements were tested for an association to injury using logistic regression analysis. Results: Incidence rates for MTSS were 2.7/1,000 AEs, 3.9/1,000 AEs, and 1.7/1,000 AEs for all subjects, girls, and boys, respectively. After logistic regression modeling, only gender was found to be significantly related with the occurrence of MTSS, as girls were 3.3 times more likely than boys to develop MTSS during the cross country season. No significant associations were found between MTSS and either navicular drop or foot length. Conclusions: The results of this study reveal that the incidence of MTSS is greater among female runners than male runners. Furthermore, our findings indicate that navicular drop may not be an appropriate measure to identify runners who may develop MTSS during a cross country season. Clinical Relevance: Similar to other sports, female cross country runners experience a greater incidence of injury than male runners. Current training programs aimed at reducing the risk of injury to female athletes may prove useful among cross country runners. As navicular drop was not useful in predicting the occurrence of MTSS, additional studies are needed to identify appropriate preseason screening tools.