PURPOSE: Information regarding antimicrobial prophylaxis (AMP) for gastric cancer surgery is limited. The present study investigated the efficacy of single-dose AMP for the prevention of surgical site infection (SSI) in patients undergoing gastrectomy for gastric carcinoma. MATERIALS AND METHODS: Between 2011 and 2013, 1,330 gastric carcinoma surgery patients were divided into two AMP administration groups depending on the duration of treatment. Postoperative outcomes including morbidity and SSI were compared between the two groups overall and in matched patients. Risk factors for SSI were analyzed. RESULTS: The extended group (n=1,129) received AMP until postoperative day 1 and the single-dose group (n=201) received singledose AMP only during an operation. Postoperatively, there were no significant differences between the two groups with respect to overall morbidity, mortality, or length of hospital stay. The SSI rate of the single-dose group was not significantly different from that of the extended group overall (4.5% vs. 5.5%, respectively, P=0.556) or in matched patients (4.5% vs. 4.0%, respectively, P=0.801). There was no increase in the SSI rate of the single-dose group compared to the extended group in subgroups based on different clinicopathological and operative factors. Univariate and multivariate analyses revealed male gender, open surgery, and operating time (> or =180 minutes) as independent risk factors for SSI. CONCLUSIONS: Single-dose AMP showed no increase in the postoperative SSI rate compared to postoperative extended use in patients undergoing gastrectomy for gastric carcinoma. The efficacy of single-dose AMP requires further investigation in randomized clinical trials specific to gastric cancer surgery.