We investigated the post-operative surgical site infection (SSI) rate in oral cavity cancer patients who had previous operation in the oral cavity region and compared it with that of patients without previous operation. We retrospectively reviewed over 1,000 chart records of oral cavity cancer patients from January 2004 to November 2010 and relevant data were collected. Statistical methods included descriptive statistics, bivariate analyses, and a multiple logistic regression model for investigating the relevant factors of post-operative SSI. A total of 894 patients were enrolled in the final analyses. The overall post-operative SSI rate was 20.8%. Previous history of operation was identified in 173 patients (19.4%). There was no significant difference in post-operative SSI rate between the patients with previous operation and those without (22.5 vs. 20.4%, P = 0.601). Previous operation in the oral cavity region was not associated with increased post-operative SSI rate in oral cavity cancer patients.