PURPOSE/BACKGROUND: During the 2013-14 school year, over 763,000 female athletes participated in interscholastic running sports in the United States. Recent studies have indicated associations between the female athlete triad (Triad) and stress fracture or other musculoskeletal injuries in elite or collegiate female running populations. Little is known about these relationships in an adolescent interscholastic running population. The purpose of this study was to determine the associations between Triad and risk of lower extremity musculoskeletal injury among adolescent runners. METHODS: Eighty-nine female athletes competing in interscholastic cross-country and track in southern California were followed, prospectively. The runners were monitored throughout their respective sport season for lower extremity musculoskeletal injuries. Data collected included daily injury reports, Eating Disorder Examination Questionnaire (EDE-Q) that assessed disordered eating attitudes/behaviors, a questionnaire on menstrual history and demographic characteristics, a dual-energy x-ray absorptiometry scan that measured whole-body bone mineral density (BMD) and body composition (lean tissue and fat mass), and anthropometric measurements. RESULTS: Thirty-eight runners (42.7%) incurred at least one lower extremity musculoskeletal injury. In the BMD Z-score ≤ -1 standard deviation (SD) adjusted model, low BMD relative to age (BMD Z-score of ≤ -1SD) was significantly associated (Odds Ratio [OR]=4.6, 95% confidence interval [CI]: 1.5-13.3) with an increased occurrence of musculoskeletal injury during the interscholastic sport season. In the BMD Z-score ≤ -2 SDs adjusted model, a history of oligo/amenorrhea was significantly associated (OR=4.1, 95% CI: 1.2-13.5) with increased musculoskeletal injury occurrence. CONCLUSION: Oligo/amenorrhea and low BMD were associated with musculoskeletal injuries among the female interscholastic cross-country and track runners. CLINICAL RELEVANCE: Regular, close monitoring of adolescent female runners during seasonal and off-season training may be warranted, so that potential problems can be recognized and addressed promptly in order to minimize the risk of running injury. LEVEL OF EVIDENCE: 2.