This prospective study of 583 habitual runners used baseline information to examine the relationship of several suspected risk factors to the occurrence of running-related injuries of the lower extremities that were severe enough to affect running habits, cause a visit to a health professional, or require use of medication. During the 12-month follow-up period, 252 men (52%) and 48 women (49%) reported at least one such injury. The multiple logistic regression results identified that running 64.0 km (40 miles) or more per week was the most important predictor of injury for men during the follow-up period (odds ratio = 2.9). Risk also was associated with having had a previous injury in the past year (odds ratio = 2.7) and with having been a runner for less than 3 years (odds ratio = 2.2). These results suggest that the incidence of lower-extremity injuries is high for habitual runners, and that for those new to running or those who have been previously injured, reducing weekly distance is a reasonable preventive behavior.