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Background: The liver is the site of distant failure in > 33% of patients with colorectal adenocarcinoma. Liver resection is the only potentially curative option in these patients. Patients with incompletely resected liver lesions (due to the proximity to critical vascular structures) are at high risk of dying of progressive disease in the liver. This pilot study was performed to determine whether the intraoperative implantation of iodine-125 (I-125) seeds could reduce the recurrence and improve the survival of patients with incompletely resected liver metastases., Methods: Fifty-six patients with unresectable or residual disease after surgical resection of liver metastases from colorectal carcinoma underwent permanent implantation with I-125 seeds to deliver 160 gray to the periphery of the target volume., Results: The 1-, 3-, and 5-year actuarial control rates of liver disease were 41%, 23%, and 23%, respectively. The 5-year actuarial control of liver disease was better for patients with a solitary metastasis (39%) than for those with multiple metastases (9%) (P = 0.04). The 1-, 3-, and 5-year actuarial overall survival rates were 71%, 25%, and 8%, respectively (median, 20 months; 95% confidence interval, 17-23). The radiation-related complications were minimal., Conclusions: I-125 liver brachytherapy is feasible with minimal radiation-related morbidity. Good prognostic factors for long term liver control and survival are the presence of a solitary metastasis, postresection minimal residual disease requiring smaller volume implants, and no prior liver resections. Future prospective trials should be directed toward this patient population, which has the highest probability of obtaining improved results from the local dose escalation provided by brachytherapy. Adjuvant regional chemotherapy clearly is needed due to the high rate of liver recurrence and ultimate death from liver failure observed in spite of liver resection and brachytherapy.