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The aim of this study was to determine whether anastomotic leakage has an independent association with overall survival and cancer-specific survival.There are many known prognostic indicators following surgery for colorectal cancer (CRC). However, the impact of anastomotic leakage has not been adequately assessed.Consecutive patients undergoing resection between 1971 and 1999 were recorded prospectively in the Concord Hospital CRC database. Total anastomotic leakage was defined as any leak, whether local, general, or radiologically diagnosed. Patients were followed until death or to December 31, 2002. The association between anastomotic leakage and both overall survival and cancer-specific survival was examined by proportional hazards regression with adjustment for other patient and tumor characteristics influencing survival. Confidence intervals (CI) were set at the 95% level.From an initial 2980 patients, 1722 remained after exclusions. The total leak rate was 5.1% (CI 4.1–6.2%). In patients with a leak, the 5-year overall survival rate was 44.3% (CI 33.5–54.6%) compared to 64.0% (CI 61.5–66.3%) in those without leak. In proportional hazards regression–after adjustment for age, gender, urgent resection, site, size, stage, grade, venous invasion, apical node metastasis and serosal surface involvement–anastomotic leakage had an independent negative association with overall survival (hazard ratio [HR] 1.6, CI 1.2–2.0) and cancer-specific survival (HR 1.8, CI 1.2–2.6).Apart from its immediate clinical consequences, anastomotic leakage also has an independent negative association with survival.