BACKGROUND Anastomotic leakage is a serious complication of colorectal surgery. Several studies have demonstrated the beneficial pleiotropic effects of statins, and preliminary studies have suggested that perioperative statin treatment may be associated with reduced risk of anastomotic leakage. OBJECTIVE We aimed to investigate whether perioperative statin therapy was associated with a reduced anastomotic leakage rate after colorectal resections with primary anastomosis. DESIGN The study was based on prospectively collected data from the Danish Colorectal Cancer Group and electronically registered medical records holding information on perioperative statin therapy. SETTINGS Data were collected from the 6 major surgical centers responsible for all elective colorectal cancer surgery in the eastern part of Denmark. PATIENTS We collected data on 2766 patients with electronically registered medical records who underwent resection of the colon or rectum with primary anastomosis from 2006 to 2009. MAIN OUTCOME MEASURE The primary outcome measured was anastomotic leakage requiring surgical intervention. RESULTS Five hundred eighteen patients (19%) were treated with statins perioperatively. Four hundred ninety-six patients received statins both before and after surgery. Fifty-two patients (10.5%) received high-dose statin therapy. Possible risk factors for anastomotic leakage were identified via univariate regression analyses. In subsequent multivariate analysis, perioperative statin therapy was not associated with reduced anastomotic leakage rate (OR (95% CI) 1.31 (0.84-2.05), p = 0.23). We identified intraoperative blood transfusion, rectal resection (versus colonic), male sex, and tobacco usage as risk factors for anastomotic leakage in the multivariate analysis. LIMITATIONS This study is limited by its observational design and missing data on comorbidities and BMI. CONCLUSION Perioperative statin therapy was not significantly associated with reduced anastomotic leakage rate after colorectal resection with primary anastomosis.