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To determine if measurable lower extremity alignment is a risk factor for overuse running injuries.Prospective cohort study.Thirty-two week marathon training program.Three hundred fifty-five volunteers from the marathon training program began the study; 255 finished the study.None.Past training and injury history was determined by questionnaire, and five lower extremity alignment measures were performed at the beginning of the training program: arch index (AI), heel valgus (HV), knee tubercle-sulcus angle (TSA), knee varus (KV), and leg-length difference (LLD). Overuse injuries, incurred by the runners and categorized by anatomic parts, were recorded during the training period.Ninety subjects experienced overuse injuries. Multivariate analyses with stepwise Poisson regression showed few consistent relationships between alignment and overuse injury rates. Higher AI was protective against overall injuries and knee injuries; higher HV was protective against knee and foot injuries; higher TSA was associated with shin injuries; higher KV was associated with shin injuries; and low LLD was associated with more overall injuries.Minor variations in lower extremity alignment do not appear conclusively to be major risk factors for overuse injuries in runners. Because of the study limitations and the likely multifactorial nature of running injuries, further study is suggested, perhaps in more novice runners.