BACKGROUND: Only a minority of patients are suitable for liver resection for colorectal liver metastases. Cryotherapy was the first widely used ablative technique, achieving a median survival of more than 2 years. Patient selection is important, but the prognostic criteria have been controversial. The combined treatment modality of cryotherapy, resection, and hepatic arterial chemotherapy has been used in treating unresectable liver disease. Many centers would not surgically treat patients with multiple (five or more lesions) bilateral liver metastases. This series reports on longterm results after cryotherapy and hepatic arterial chemotherapy with or without liver resection in 224 patients with colorectal liver metastases, especially in patients with multiple bilateral liver disease, and identifies important prognostic determinants for survival. STUDY DESIGN: A longterm retrospective analysis was performed of prospectively collected clinical data of 224 patients with colorectal liver metastases who received cryotherapy and hepatic arterial chemotherapy with or without resection. Morbidity, mortality, recurrence, and survival rates were reported and Kaplan-Meier and Cox regression analysis were used to identify prognostic indicators. RESULTS: Median length of followup was 26 months (range 1 to 130 months). Perioperative mortality rate was 0.4% and morbidity rate was 21%. Cryosite, remaining liver, and extrahepatic recurrence rates were 39%, 62%, and 67%, respectively. Median survival was 31 months (range 1 to 130 months) with 1-, 3-, and 5-year survival rates of 87%, 43%, and 23%, respectively. Ninety-one patients had five or more bilateral lesions. Median and 5-year survival was 31 months (2 to 88 months) and 26%, respectively. Four factors were independently associated with favorable survival outcomes: cryotherapy with resection, complete tumor eradication, low pre- and postoperative CEA levels. CONCLUSIONS: Cryotherapy and hepatic arterial chemotherapy with or without resection can achieve long survival advantage in patients with unresectable colorectal liver metastases.