OBJECTIVE : Infectious complications in open lower extremity fractures contribute to significant morbidity. Historically, orthopedic guidelines have recommended Grade III fractures receive a first generation cephalosporin and an aminoglycoside. Despite these guidelines, few studies have evaluated the utility of adding an aminoglycoside in this patient population. At our trauma center, we have a unique trauma service where half of our surgeons treat Grade III open fractures with a cephalosporin alone and half use a cephalosporin + aminoglycoside. We hypothesized that our outcomes were the same between the two groups. METHODS : We identified all Grade III fractures of the lower extremity admitted to our urban Level I Trauma Center over the 5-year study period. Charts were retrospectively reviewed to identify demographic information, injury severity score (ISS), fracture location, grade of fracture, type of antibiotic administered, incidence of acute kidney injury (AKI), surgical site infection (SSI), hardware removal, hospital length of stay (HLOS), and disposition. Patients were classified into two groups: those treated with a cephalosporin alone (CEPH) or cephalosporin + an aminoglycoside (CEPH + AG). RESULTS : A total of 126 grade III fractures of the lower extremity were admitted our Trauma Center during the 5-year study period. There were 65 (52%) patients in the CEPH group and 61 (48%) in the CEPH + AG group. Demographics, ISS, fracture location, grade of fracture, rate of SSI, need for hardware removal, and disposition were not different between the two groups. In contrast, patients in the CEPH group had a 4% incidence of AKI, while the incidence was 10% of patients in the CEPH + AG group (p < 0.05). CONCLUSIONS : The addition of an AG to antibiotic prophylaxis in open lower extremity fractures was associated with a significant increase in AKI with no change in the incidence of wound infection or hardware removal. Cephalosporins alone may be sufficient for prophylaxis in Grade III open fractures of the lower extremity. A large-scale prospective randomized trial is needed to confirm these findings and inform clinical practice.