Purpose: The aim of this was to assess potential risk factors for anastomotic dehiscence in colon cancer surgery in a national cohort. Methods: All patients, who had undergone a resection of a large bowel segment with an anastomosis between 2008 and 2011, were identified in the Swedish Colon Cancer Registry. Patient factors, socioeconomic factors, surgical factors, and medication and hospital data were combined to evaluate risk factors for anastomotic dehiscence. Results: The prevalence of anastomotic dehiscence was 4.3 % (497/11 565). Male sex, ASA classification III–IV, prescribed medications, bleeding more than 300 mL, and uncommon colorectal resections were associated with a higher risk of anastomotic dehiscence. Hospital stay was increased with 14.5 days, and 30-day mortality as well as long-term mortality was higher in the anastomotic dehiscence group. Conclusions: There are several factors that are possible to know preoperatively or during surgery that can indicate whether an anastomosis is an appropriate option. Anastomotic dehiscence increases hospital stay and long-term mortality.