Forty-two patients with acute open femoral shaft fractures were assigned prospectively to primary immediate or delayed reamed intramedullary stabilization. There were 27 primary and 15 delayed intramedullary nailings performed (mean followup, 20 months). Twelve patients (29%) had Gustilo and Anderson Grade I injury; 16 (38%), Grade II; and 14 (33%), Grade III (including 3 Grade IIIC). Average time to union was 3.8 months. The infection and nonunion rate was 2.4%. Comparison of the 2 groups showed no significant differences in the incidence of infection, malunion, nonunion, or the time to union. The data suggest that primary reamed intramedullary nailing is an effective treatment alternative for the patient with multiple injuries, regardless of soft tissue injury, including Grade III wounds. Isolated open femoral shaft fractures with Grade I and Grade II soft tissue wounds may be stabilized safely primarily with no increased morbidity. Although results were promising, continued study is needed to delineate the optimum management of all Grade III injuries.