This study critically evaluated the prognostic determinants for disease-free survival (DFS) after cryoablation for colorectal liver metastases. An observational cohort study of prospectively collected data on 135 patients who underwent cryoablation with or without resection for colorectal liver metastases was performed. Univariate and multivariate analyses were used to determine the prognostic factors for overall DFS, cryosite DFS, remaining liver DFS, and extrahepatic DFS. Overall, 115 patients (85%) developed recurrence at the cryosite (44%), and the remaining patients developed recurrence at the liver (62%) and extrahepatic site (71%). In univariate analysis, preoperative and postoperative carcinoembryonic antigen (CEA) were significant for overall DFS. Distribution of metastases, operation type, total number of metastases, number of cryotreated metastases, largest size of cryotreated metastasis, and postoperative CEA were significant for cryosite DFS. The number of cryotreated metastases and postoperative CEA were significant for remaining liver DFS. The largest size of cryotreated metastasis, and preoperative and postoperative CEA were significant for extrahepatic DFS. In multivariate analysis, resection plus cryoablation, < or =7 liver metastases and < or =3 cm cryotreated metastasis were independently associated with an improved cryosite DFS. Preoperative CEA of < or =5 ng/mL was independently associated with an improved overall and extrahepatic DFS. The role of CEA in colorectal metastasis is important. Resection plus cryoablation rather than cryoablation alone should be used for larger lesions.