Radiofrequency ablation (RFA) is a safe and effective treatment in patients with unresectable liver malignancies. Since there is little information on its optimal approach, the feasibility, clinical outcome, and efficacy of laparoscopic RFA need further investigation. Twenty-three consecutive patients with unresectable hepatic malignancies were treated with RFA. RFA was performed percutaneously in 5 patients (5 tumors; median maximum diameter of 25 mm [range, 20-73]), via laparotomy in 9 (28 tumors; median maximum diameter of 38 mm [5-90]), and via laparoscopy in 9 (16 tumors; median maximum diameter of 35 mm [8-58]). Mortality and intraoperative complication rates were 0. In the laparoscopy and laparotomy groups, mean blood loss was 13 mL versus 421 mL and mean hospital stay was 5.7 versus 11.2 days, respectively (P = 0.0008 and P = 0.04). Postoperative complications occurred in one patient after laparoscopic RFA and in three after RFA via laparotomy. After a median follow-up of 12.2 months, local recurrence occurred in 2 patients (laparoscopic RFA, 1; percutaneous RFA, 1), and new hepatic tumors developed in 7 (laparoscopic RFA, 2/9; RFA via laparotomy, 5/9). Laparoscopic RFA is a safe and feasible treatment modality to achieve tumor destruction in selected patients with unresectable hepatic malignancies.