Background: The purpose of this study was to compare risk factors for the development of incisional versus organ/space infections in patients undergoing colorectal surgery. Methods: An institutional review board-approved retrospective review was performed examining a 4-year period (January 2002 to December 2005). Patients were included if they had undergone abdominal operations (open or laparoscopic) in which the colon/rectum was surgically manipulated. Patients were excluded if the surgical wound was not closed primarily. A standardized definition of incisional and organ/space infection was employed. Results: A total of 428 operations were performed. Overall, 105 infections were identified (25%); 73 involved the incision and 32 were classified as organ/space. Multivariate analysis suggested that incisional infection was independently associated with body mass index (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02-1.11) and creation/revision/reversal of an ostomy (OR, 2.2; 95% CI, 1.3-3.9). Organ/space infection was independently associated with perioperative transfusion (OR, 2.3; 95% CI, 1.1-5.5) and with previous abdominal surgery (OR, 2.5; 95% CI, 1.2-5.3). Conclusions: Factors associated with infection differed based on the type of surgical site infection being considered. The lack of overlap between factors associated with incisional infection and organ/space infection suggests that separate risk models and treatment strategies should be developed.