Cryotherapy is undergoing a renaissance in the treatment of nonresectable liver tumors. In a prospective case control study we assessed the morbidity, mortality, and efficacy of hepatic cryotherapy for liver metastases. Between January 1996 and September 1999 a total of 54 cryosurgical procedures were performed on 49 patients (median age 66 years, 21 women) with liver metastases. Patient, tumor, and operative details were recorded prospectively. Liver metastases originated from colorectal cancer (n=37), gastric cancer (n=3), renal cell carcinoma (n=2), and other primaries (n=7). Median follow-up was 13 months (1-32). The median number of liver metastases was 3 (range 1-10) with a median diameter of 3.9 cm (range 1.5-11). Twenty-one patients (43%) had cryoablation only, and 28 (57%) had liver resection in combination with cryoablation. One patient (2%) died within 30 postoperative days. Another 13 patients (27%) developed reversible complications. In 19 of 25 patients (76%) with preoperatively elevated serum CEA and colorectal metastases it returned to the normal range postoperatively. Twenty-eight patients (57%) developed tumor recurrence, eight of which with involvement of the cryosite. Overall median survival patients was 23 months, and survival in patients with colorectal metastases was 29 months. Hepatic cryotherapy is associated with tolerable morbidity and mortality. Efficacy is demonstrated by tumor marker results. Survival data are promising; however, long-term results must be provided to allow comparison with other treatment modalities.