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The aim of this study was to compare single-incision laparoscopic colectomy (SILC) to multiport laparoscopic colectomy (MLC) when performed by experienced laparoscopic surgeons.Recent case reports and single institution series have demonstrated the feasibility of SILC. Few comparative studies for MLC and SILC have been reported.Patients from 5 institutions undergoing SILC were entered into an IRB approved database from November 2008 to March 2010. SILC patients were matched with those undergoing MLC for gender, age, disease, surgery, BMI, and surgeon. The primary endpoint was length of stay and secondary endpoints included operative time, conversion, complications and postoperative pain scores.Three hundred thirty patients (SILC = 165, MLC = 165) were evaluated. Operative time (135 ± 45 min vs. 133 ± 56 min; P = 0.85) and length of stay (4.6 ± 1.6 vs. 4.3 ± 1.4; P = 0.35) were not significantly different. Maximum postoperative day one pain scores were significantly less for SILC (4.9 vs. 5.6; P = 0.005). Eighteen (11%) patients undergoing SILC were converted to multiport laparoscopy. There was no statistical difference between groups for conversions to laparotomy, complications, re-operations, or re-admissions.SILC is feasible when performed on select patients by surgeons with extensive laparoscopic experience. Outcomes were similar to MLC, except for a reduction in peak pain score on the first postoperative day. Prospective randomized trials should be performed before incorporation of this technology into routine surgical care.