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To assess factors affecting long-term survival of patients undergoing radiofrequency ablation (RFA) of colorectal hepatic metastases, with attention to evolving chemotherapy regimens.Prospective evaluation of 235 patients with colorectal metastases who were not candidates for resection and/or failed chemotherapy underwent laparoscopic RFA. Preoperative risk factors for survival and pre- and postoperative chemotherapy exposure were analyzed.Two hundred and thirty-four patients underwent 292 RFA sessions from 1997 to 2006, an average of 8 months after initiation of chemotherapy. Twenty-three percent had extrahepatic disease preoperatively. Patients averaged 2.8 lesions, with a dominant diameter of 3.9 cm. Kaplan-Meier actuarial survival was 24 months, with actual 3 and 5 years survival of 20.2% and 18.4%, respectively. Median survival was improved for patients with ≤3 versus >3 lesions (27 vs. 17 months, P = 0.0018); dominant size <3 versus >3 cm (28 vs. 20 months, P = 0.07); chorioembryonic antigen <200 versus >200 ng/mL (26 vs. 16 months, P = 0.003). Presence of extrahepatic disease (P = 0.34) or type of pre/postoperative chemotherapy (5-FU-leucovorin vs. FOLFOX/FOLFIRI vs. bevacizumab) (P = 0.11) did not alter median survival.To our knowledge, this is both the largest and longest follow-up of RFA for colorectal metastases. The number and dominant size of metastases, and preoperative chorioembryonic antigen value are strong predictors of survival. Despite classic teaching, extrahepatic disease did not adversely affect survival. In this group of patients who failed chemotherapy, newer treatment regimens (pre- or postoperatively) had no survival benefit. The actual 5-year survival of 18.4% in these patients versus near zero survival for chemotherapy alone argues for a survival benefit of RFA.