OBJECTIVE: We evaluated the feasibility, tolerance, and efficacy of percutaneous hepatic vein or segmental portal branch balloon occlusion during radiofrequency ablation of hepatic malignancies. SUBJECTS AND METHODS: Ten tumors were treated by percutaneous radiofrequency ablation during balloon occlusion of a hepatic vein (n = 8) or a segmental portal branch (n = 2). Venous occlusion was undertaken because the tumor was in contact with a hepatic vein (n = 3) or a portal branch (n = 1); because the tumor exceeded 35 mm in width (mean, 44 mm), which was considered the maximum size amenable to ablation in a single session (n = 2); or because of both large size and contact with a hepatic vein (n = 3) or a portal branch (n = 1). RESULTS: Vascular occlusion was always technically possible. Radiofrequency was delivered to one to three locations (mean, 1.9 locations) with a cluster electrode. The largest axis of radiofrequency-induced lesions after ablation with the cluster needle-between 42 and 51 mm (mean, 49 mm)-was always larger than the targeted tumor. These sizes were statistically larger than in a matched control group of patients who underwent radiofrequency ablation without vascular occlusion (p < 0.0003). After a mean follow-up of 12.6 months, CT and MR imaging revealed complete destruction of nine tumors after a single radiofrequency ablation treatment; one tumor required three treatments to achieve ablation. Five patients are tumor-free 12-18 months (mean, 14.4 months) after the first radiofrequency ablation treatment, and five developed new liver metastases. CONCLUSION: Temporary hepatic vein or portal branch occlusion during radiofrequency ablation can safely facilitate the treatment of large tumors or tumors in contact with the walls of large vessels.