BACKGROUND: Anastomotic dehiscence is the most severe surgical complication after large bowel resection. This study was designed to assess the incidence, to observe the consequences, and to identify the risk factors associated with anastomotic leakage after colorectal surgery. MATERIALS AND METHODS: All procedures involving anastomoses of the colon or the rectum, which were performed between November 2002 and February 2006 in a single institution, were prospectively entered into a computerized database. RESULTS: One thousand eighteen colorectal resections and 811 anastomoses were performed over this 40-month period. The most frequent procedures were sigmoid (276) and right colectomies (217). The overall anastomotic leak rate was 3.8%. The mortality rate associated with anastomotic leak was 12.9%. In univariate analysis, the following parameters were associated with an increased risk for anastomotic dehiscence: (1) ASA score >or= 3 (p = 0.004), (2) prolonged (>3 h) operative time (p = 0.02), (3) rectal location of the disease (p < 0.001), (4) and a body mass index > 25 (p = 0.04). In multivariate analysis, ASA score >or= 3 (OR = 2.5; 95% CI 1.5-4.3, p < 0.001), operative time > 3 h [OR = 3.0; 95% CI 1.1-8.0, p = 0.02), and rectal location of the disease (OR = 3.75; 95% CI 1.5-9.0 (vs left colon), p = 0.003; OR = 7.69; 95% CI 2.2-27.3 (vs right colon), p = 0.001] were factors significantly associated with a higher risk of anastomotic dehiscence. CONCLUSIONS: Three risk factors for anastomotic leak have been identified, one is patient-related (ASA score), one is disease-related (rectal location), the third being surgery-related (prolonged operative time). These factors should be considered in perioperative decision-making regarding defunctioning stoma formation.