Objectives: To examine the prophylactic antibiotic use in reducing surgical site infection. Methods: This was a retrospective study for patients aged 18 years and older who underwent gastrectomy, cholecystectomy, colectomy, cesarean section and hysterectomy. The data source was quality assessment data of the Health Insurance Review & Assessment Service gathered from medical records of 302 national hospitals. Prophylactic antibiotic use was defined as: timely antibiotic administration or inappropriate antibiotic selection. We performed hierarchical logistic regression to examine the association between prophylactic antibiotic use and surgical site infection with adjustment for covariates. Results: The study population consisted of 16 348 patients (1588 gastrectomies, 2327 cholecystectomies, 1,384 colectomies, 3977 hysterectomies and 7072 cesarean sections) and surgical site infection was identified in 351 (2.1%) patients. The rates of timely antibiotic administration and inappropriate antibiotic selection varied according to procedures. Cholecystectomy patients who received timely prophylactic antibiotic had a significantly reduced risk of surgical site infection compared with those who did not receive a timely prophylactic antibiotics (OR 0.64, 95% CI=0.50-0.83), but no significant reduction was observed for other procedures. When inappropriate prophylactic antibiotics were given, the risk of surgical site infection significantly increased: 8.26-fold (95% CI=4.34-15.7) for gastrectomy, 4.73-fold (95% CI=2.09-10.7) for colectomy, 2.34-fold (95% CI=1.14-4.80) for cesarean section, 4.03-fold (95% CI=1.93-8.42) for hysterectomy. Conclusions: This study examines the association among timely antibiotic administration, inappropriate antibiotic selection and surgical site infection. Patients who received timely and appropriate antibiotics had a decreased risk of surgical site infection. Efforts to improve the timing of antibiotic administration and use of appropriate antibiotic are needed to lower the risk of surgical site infection.