OBJECTIVES: (1) To determine the overall treatment costs associated with isolated low-energy gunshot wounds (GSWs) to the extremity and (2) to estimate cost savings associated with a single-dose IV antibiotic strategy administered in the emergency room for patients with simple GSWs. DESIGN: Retrospective review. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Patients (N = 380) with extremity-only GSW injuries from 2010 to 2015 were retrospectively reviewed. Treatment was recorded including type and duration of antibiotics, admission, and surgical intervention. MAIN OUTCOME MEASURES: Costs were calculated including facility services in the operating room and hospital. RESULTS: There were 460 GSWs in 380 patients with a mean age of 30 years old. There were 309 admissions, 273 operations performed, and 1010 days of antibiotics prescribed. The total inpatient facility cost to treat all patients was $1,701,154. Among 179 patients who could be treated by the single-dose antibiotic care pathway for simple GSWs, 132 patients (73%) received additional treatment with 108 hospital admissions, 26 debridement surgeries, and 322 days of additional oral and/or IV antibiotics. The single-dose antibiotic care pathway would have saved an average of $1436 per patient with simple GSWs in actual facility expenses. CONCLUSIONS: The overall cost associated with isolated low-energy GSWs to the extremity is high. Limiting antibiotics to a single IV dose in the emergency room can reduce treatment expenses substantially for patients with simple GSWs. LEVEL OF EVIDENCE: Economic Level IV. See instructions for authors for a complete description of levels of evidence.