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Background: Single-incision laparoscopic cholecystectomy (SILC) may be a comparable alternative to conventional multiport laparoscopic cholecystectomy (LC). This study compared procedural outcomes and costs between SILC and LC., Methods: A retrospective review of patients undergoing SILC over an 8-month period was performed. A cohort of LC patients from the same surgeons over the preceding 8 months was used as historic controls. Demographics, comorbidities, diagnosis, operative data, pain control in the recovery room, complications, length of hospital stay, and cost were compared between the two groups., Results: Of the 285 patients, 177 underwent LC and 108 underwent SILC. The mean age was 49.7 years for the LC patients and 48.2 years for the SILC patients (p = 0.44). Two of the LC patients underwent conversion to open surgery. None of SILC patients were converted to open procedure, although nine had additional ports placed. After multivariate adjustment, SILC was associated with a 15% longer operative time (p = 0.053) and a 66% shorter hospital stay (p = 006) than LC. Biliary dyskinesia and biliary colic were independently associated with shorter operative times and a reduced hospital stay. No significant differences were noted in pain score, narcotics used in the postanesthesia care unit (PACU), 30-day complication rates (1.7 vs 1.9%; p = 1), hospital charges, or cost between the two groups., Conclusions: Single-incision LC is safe, significantly reduces the hospital stay, and is an acceptable alternative to traditional LC. Although further study is warranted, initial results indicate that SILC may offer the most benefit for outpatient procedures.