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PURPOSE: Surgical site infection (SSI) is a major concern in colorectal surgery (CRS). It accounts for 60 % of all postoperative complications and has an incidence of between 10 and 30 %. The gentamicin-collagen sponge (GCS) was developed to help avoid SSI. The aim of this study was the evaluation of the efficacy of a GCS in preventing SSI after CRS. METHOD: This study was a retrospective analysis of data collected in a prospective database. Six hundred six CRS patients were enrolled in the study and prospectively assigned to one of two groups. From January 2007 to December 2008, all procedures were performed without the use of GCS (forming the non-GCS group). From January 2009 to July 2011, all procedures included a GCS (forming the GCS group). The primary endpoint was the presence or absence of SSI at postoperative day 30. RESULTS: The incidence of SSI was 29.7 and 20.8 % in the non-GCS and GCS groups, respectively (p = 0.019). By using a stepwise logistic regression, the predictors of SSI were found to be ASA grade (p < 0.001), operating time (log-transformed value, p < 0.001), gender (p = 0.021), and GCS use (p < 0.001). By adjusting on these variables, a mean reduction in postoperative hospitalization of 8.3 days was found in the GCS group. The proportions of Clavien IIIB-V were 16.6 and 8.9 % for the non-GCS and GCS groups, respectively (p = 0.041). CONCLUSIONS: This study provides additional evidence of the efficacy of the GCS in reducing SSI rates and shortening hospitalization after CRS.