Objective:The aim of this study was to evaluate oncological outcome for patients with and without anastomotic leakage after colon or rectal cancer surgery.Summary of Background Data:The role of anastomotic leakage in oncological outcome after colorectal cancer surgery is still topic of debate and impact on follow-up and consideration for further treatment remains unclear.Methods:Patients included in the international, multicenter, non-inferior, open label, randomized, controlled trials COLOR and COLOR II, comparing laparoscopic surgery for curable colon (COLOR) and rectal (COLOR II) cancer with open surgery, were analyzed. Patients operated by abdominoperineal excision were excluded. Both univariate and multivariate analyses were performed to investigate the impact of leakage on overall survival, disease-free survival, local and distant recurrences, adjusted for possible confounders. Primary endpoints in the COLOR and COLOR II trial were disease-free survival and local recurrence at 3-year follow-up, respectively, and secondary endpoints included anastomotic leakage rate.Results:For colon cancer, anastomotic leakage was not associated with increased percentage of local recurrence or decreased disease-free-survival. For rectal cancer, an increase of local recurrences (13.3% vs 4.6%; hazard ratio 2.96; 95% confidence interval 1.38-6.34; P = 0.005) and a decrease of disease-free survival (53.6% vs 70.9%; hazard ratio 1.67; 95% confidence interval 1.16-2.41; P = 0.006) at 5-year follow-up were found in patients with anastomotic leakage.Conclusion:Short-term morbidity, mortality, and long-term oncological outcomes are negatively influenced by the occurrence of anastomotic leakage after rectal cancer surgery. For colon cancer, no significant effect was observed; however, due to low power, no conclusions on the influence of anastomotic leakage on outcomes after colon surgery could be reached. Clinical awareness of increased risk of local recurrence after anastomotic leakage throughout the follow-up is mandatory.Trial Registration: Registered with ClinicalTrials.gov, number NCT00387842 and NCT00297791.