Background Increasing the drug concentration in tumors may produce massive tumoral response. By using a variety of hepatic vascular isolation techniques, high concentrations of chemotherapeutic drugs may be achieved in the hepatic vascular bed. Hypothesis Complete percutaneous isolated hepatic perfusion (IHP) is feasible and safe. Design Case series. Setting The hepatobiliary unit of a university hospital. Patients Ten patients with irresectable and chemoresistant hepatic tumors were eligible for study participation; 4 patients with hepatic metastases of breast cancer, gastric cancer, colorectal cancer, and cholangiocarcinoma were included. Intervention Patients received 3 successive courses of chemotherapy by IHP. The first course was given at laparotomy, and the next 2 courses were given percutaneously. The interval between courses was 3 to 6 weeks. Each course involved IHP of the liver for 15 to 30 minutes, without oxygenation, with 1 to 3 boluses of melphalan (15 mg). Main Outcome Measures Morbidity and mortality. Results Ten IHPs were performed (4 at laparotomy and 6 percutaneously). Concentrations of melphalan in the extracorporeal circulation were 10 times higher than those in the systemic circulation. Percutaneous IHPs had more leakage than those at laparotomy. However, hepatotoxicity was minimized. One patient experienced hepatic artery thrombosis, and 3 had severe neutropenia. Minor complications included ascites and pleural effusion. No deaths were observed 2 months after the last IHP. One partial response was observed (hepatic metastases of breast cancer). Conclusion Percutaneous IHP for intensive chemotherapy is less aggressive and less hepatotoxic than IHP at laparotomy and may be iterative.