Introduction There are no definitive data concerning the ideal configuration of ileocolic anastomosis. Aim of this study was to identify perioperative risk factors for anastomotic leak and for 60-day morbidity and mortality after ileocolic anastomoses (stapled vs handsewn). Materials and methods This is a STROBE-compliant study. Demographic and surgical data were gathered from patients with an ileocolic anastomosis performed between November 2010 and September 2016 at a tertiary hospital. Anastomoses were performed using standardised techniques. Independent risk factors for anastomotic leak, complications and mortality were assessed. Results We included 477 patients: 53.7% of the anastomoses were hand sewn and 46.3% stapled. Laterolateral anastomosis was the most common configuration (93.3%). Anastomotic leak was diagnosed in 8.8% of patients and 36 were classified as major anastomotic leak (7.5%). In the multivariate analysis, male sex (P = 0.014, odds ratio, OR, 2.9), arterial hypertension (P = 0.048, OR 2.29) and perioperative transfusions (P < 0.001, OR 2.4 per litre) were independent risk factors for major anastomotic leak. The overall 60-day complication rate was 27.3%. Male sex (31.3% vs female 22.3%, P = 0.02, OR 1.7), diabetes (P = 0.03 OR 2.0), smoking habit (P = 0.04, OR 1.8) and perioperative transfusions (P < 0.001, OR 3.3 per litre) were independent risk factors for postoperative morbidity. The 60-day-mortality rate was 3.1% and no significant risk factors were identified. Conclusion Anastomotic leak after ileocolic anastomosis is a relevant problem. Male sex, arterial hypertension and perioperative transfusions were associated with major anastomotic leak. Conversion to open surgery was more frequently associated with perioperative death.