A secondary analysis of the Fluid Lavage of Open Wounds (FLOW) Trial database was performed to assess the effectiveness of antibiotics alone in treating superficial surgical site infection in patients who were operatively treated for open fractures. A logistic binary regression analysis was performed to identify any factors associated with antibiotic treatment failure. Of the 139 patients who received antibiotics alone for superficial surgical site infection, 97 (69.8%) were successfully treated. Delay in diagnosing superficial surgical site infection was associated with a higher odds of treatment failure (OR=1.05 per week of diagnosis delay [95%CI 1.004, 1.099], p=0.03). Age, sex, fracture severity, fracture pattern, wound size, and time from injury to initial surgical irrigation and debridement were not associated with antibiotic treatment failure.