Although preoperative antibiotics are used routinely in ankle fracture surgery, there is considerable variability in postoperative antibiotic dosing regimens amongst surgeons. The aim of this study is to compare the rate of surgical site infection (SSI) in patients receiving one dose of preoperative antibiotics to patients who received more than one dose of antibiotics. A single-center Level I Trauma Center retrospective review of patients with isolated closed ankle fractures who underwent open reduction internal fixation over a 10-year period was performed. Demographics data and risk factors were obtained from the electronic medical record. SSI was detected using a text-mining algorithm on all postoperative clinic notes. Factors associated with the development of SSI or increased antibiotic dosing were evaluated. Eight-hundred and twenty-six patients were included in the analysis. There was no correlation between infection rate and any of the potential risk factors evaluated. Two-hundred and ninety-two patients received only one dose of antibiotics preoperatively and 534 patients received more than one antibiotic dose. The rate of SSI was not significantly different between the single-dose cohort (5.8 %) and the multi-dose cohort (3.9 %) (p=0.215). Routine use of postoperative antibiotics in open reduction internal fixation of closed ankle fractures did not decrease the rate of SSI, regardless of associated comorbidities. Level of evidence: Level III (therapeutic retrospective cohort study)