OBJECTIVES: To evaluate all patients who received gentamicin for open fracture treatment and determine the incidence of, and risk factors for, kidney injury in this population. DESIGN: Retrospective, case control. SETTING: Single institution; Level 1 trauma center. PATIENTS/PARTICIPANTS: A retrospective chart review identified patients who received gentamicin for open fracture antibiotic treatment from January 2008 to December 2012. Overall, 371 patients met the inclusion criteria and were categorized into 2 groups using risk, injury, failure, loss of kidney function, and end-stage kidney disease criteria: normal kidney function (74.9%) versus abnormal kidney function (25.1%). INTERVENTION: Use of gentamicin in open fracture antibiotic treatment. MAIN OUTCOME MEASUREMENTS: Kidney function; injury and treatment characteristics (eg, mechanism of injury; Gustilo-Anderson classification; number of surgical debridements, timing of definitive wound coverage, and type of wound coverage); and patient information (eg, age, height, weight, and body mass index, tobacco use, diabetes mellitus, human immunodeficiency virus, hepatitis, and current chemotherapy treatment). RESULTS: Those with abnormal kidney function had lower baseline creatinine (P < 0.001) and higher injury severity scores (16.5 vs. 11.8, P < 0.001) and were more likely to require intensive care unit admission (P < 0.001) than the normal group. Female sex (P = 0.015), and higher weight (P = 0.004), ICU admission (P < 0.001), and use of CT contrasted imaging (P < 0.001) were independently associated with abnormal kidney function. Abnormal kidney function incidence also sharply increased with age. CONCLUSIONS: Females and heavier individuals are at-risk of kidney injury while receiving gentamicin. ICU admission and concurent CT contrasted imaging are strongly associated with kidney injury in patients receiving gentamicin for open fracture treatment, and gentamicin should be avoided in those >60 years of age. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.