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To investigate which peri-operative treatment, i.e. laparoscopic or open surgery combined with fast track or standard care, is the optimal approach for patients undergoing segmental resection for colon cancer.Patients eligible for segmental colectomy were randomized to laparoscopic or open colectomy, and to fast track or standard care, resulting in four treatment groups. Patients, nursing and medical staff were informed about the applied careprogram, but blinded to type of intervention. Primary outcome was total postoperative hospital stay. Secondary outcomes were postoperative hospital stay, morbidity, reoperation rate, readmission rate, in-hospital mortality, quality of life at 2 and 4 weeks, patient satisfaction 4 weeks postoperatively and in-hospital costs.In total 427 patients (mean age 66.5 years, 234 males) were randomized. Median total hospital stay in the laparoscopic/fast track group was 5 (interquartile range: 4-8) days; open/fast track 7 (5-11) days; laparoscopic/standard 6 (4.5-9.5) days and open/standard 7 (6-13) days (P < 0.001). Secondary outcomes did not differ significantly among the groups.Most optimal perioperative treatment for patients requiring segmental colectomy for colon cancer is laparoscopic resection embedded in a fast trackprogram. If open surgery is still applied, it ispreferentially done in fast track perioperative care.