Background. Hepatocellular carcinoma (HCC) has seen a dramatic rise in the USA over the last 30 years. Unresectable disease is present in 80Á90% of patients, for which radiofrequency ablation (RFA) is an option. The aim of this study is to report the long-term survival after laparoscopic RFA. Methods. This is a prospective analysis of 104 patients who underwent 122 ablations for unresectable HCC from April 1997 to December 2006 at a tertiary care center. Overall survival (OS) and disease-free survival (DFS) were calculated using KaplanÁMeier curves, excluding 11 patients who subsequently underwent liver transplantation. Patients were analyzed using Child-Pugh classification, Barcelona Clinic Liver Cancer (BCLC) staging and various clinical parameters. Results. Median (range) data: age 63 years (41Á81), lesion size 3.5 cm (1Á10), number of lesions 1 (1Á5), AFP 26.5 ng/ml (3.7Á43588.5) and time from diagnosis to RFA 2 months (mos) (1Á42). The median KaplanÁMeier survival for all patients was 26 mos (OS) while DFS was 14 mos. Univariate analysis demonstrated improved OS for the absence vs. presence of ascites (31 vs. 15 mos, p00.003), Bilirubin B2 mg/dl vs. ]2 mg/dl (27 vs. 19 mos, p 00.01), AFP B400 vs. ]400 (29 vs. 13 mos, p B0.0001) and Child-Pugh Grade (A028, B015, C05 mos, p0 0.01). Significant factors for improved DFS: absence vs. presence of ascites (16 vs. 5 mos, p00.02), Bilirubin B2 vs. ]2 (14 vs. 5 mos, p00.0278), AFP B400 vs. ]400 (15 vs. 4 mos, p00.0025), Child-Pugh Grade (A016, B 010, C03 mos, p 00.03). Patient age, largest tumor size, number of lesions, INR and albumin did not reach clinical significance. Three and five-year actual survival rates are 21 and 8.3%, respectively. Conclusions. Our study suggests that RFA may have a positive impact on survival for unresectable HCC. It also determines which patients fare best after RFA, by determining predictive factors that improve their survival.