BACKGROUND This study aimed to evaluate the clinicopathological factors associated with surgical site infection (SSI) and the prognostic impact on patients after colorectal cancer (CRC) resection surgery. MATERIAL AND METHODS This retrospective study evaluated the relationships between SSI and various clinicopathological factors and prognostic outcomes in 326 consecutive patients with CRC who underwent radical resection surgery at Wuhan Union Hospital during April 2015-May 2017. RESULTS Among the 326 patients who underwent radical CRC resection surgery, 65 had SSIs, and the incidence rates of incisional and organ/space SSI were 16.0% and 12.9%, respectively. Open surgery, chronic obstructive pulmonary disease (COPD), and a previous abdominal surgical history were identified as risk factors for incisional SSI. During a median follow-up of 40 months (range: 5-62 months), neither simple incisional nor simple organ/space SSI alone significantly affected disease-free survival (DFS) or overall survival (OS), whereas combined incisional and organ/space SSI had a significant negative impact on both the 3-year DFS and OS (P<0.001). A multivariate analysis identified that age ≥60 years, lymph node involvement, tumor depth (T3-T4), and incisional and organ/space SSI were independent predictors of 3-year DFS and OS. In addition, adjuvant chemotherapy and a carbohydrate antigen-125 concentration ≥37 ng/ml were also independent predictors of OS. CONCLUSIONS We have identified several clinicopathological factors associated with SSI, and identified incisional and organ/space SSI is an independent prognostic factor after CRC resection. Assessing the SSI classification may help to predict the prognosis of these patients and determine further treatment options.