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Background: Only a few series have demonstrated the safety of laparoscopic resection for hepatocellular carcinoma (HCC) and the benefits of this approach. Moreover, these studies reported mostly minor and nonanatomic hepatic resections. This report describes the results of a pair-matched comparative study between open and laparoscopic liver resections for HCC in a series of essentially anatomic resections., Methods: Patients were retrospectively matched in pairs for the following criteria: sex, age, American Society of Anesthesiology (ASA) score, severity of liver disease, tumor size, and type of resection. A total of 42 patients undergoing laparoscopy were compared with patients undergoing laparotomy during the same period. Surgeons from the authors' department not trained in laparoscopy performed open resections. Operative, postoperative, and oncologic outcomes were compared., Results: The mean duration of surgery was similar in the two groups. Significantly less bleeding was observed in the laparoscopic group (364.3 vs. 723.7 ml; p < 0.0001). Transfusion was required for four patients (9.5%) in the laparoscopic group and seven patients (16.7%) in the open surgery group (p = 0.51). Postoperative ascites was less frequent after laparoscopic resections (7.1 vs. 26.1%; p = 0.03). General morbidity was similar in the two groups (9.5 vs. 11.9%; p = 1.00). The mean hospital stay was significantly shorter for the patients undergoing laparoscopy (6.7 vs. 9.6 days; p < 0.0001). The surgical margin and local recurrence adjacent to the liver stump were not affected by laparoscopy. The overall postoperative survival rates in the laparoscopic group were 93.1% at 1 year, 74.4% at 3 years, and 59.5% at 5 years and, respectively, 81.8, 73, and 47.4% in the open surgery group (p = 0.25). The postoperative disease-free survival rates in the laparoscopic group were at 81.6% at 1 year, 60.9% at 3 years, and 45.6% at 5 years, respectively, 70.2, 54.3, and 37.2% in the open surgery group (p = 0.29)., Conclusions: Laparoscopic resection of HCC for selected patients gave a better postoperative outcome without oncologic consequences. Prospective trials are required to confirm these results.