The aim of this study was to assess the effect of vascular occlusion on radio-frequency (RF) lesion size and on potential associated biliary and portal lesions. Radio-frequency lesions using a 1-cm exposed-tip cooled electrode were created in pig liver. Liver perfusion was modified by arterial embolization (n=2), left portal clamping (n=2), and both (n=2). Two pigs were used as controls. Two weeks after, control portography was performed, animals were killed, and ex-vivo cholangiography was carried out. Pathological studies evaluated the lesion surface and associated portal and biliary damages. A mathematical regression model showed that portal occlusion increased by 43 mm2 (+40%) the surface of RF lesions, arterial occlusion by 135 mm2 (+126%), and associated occlusion by 466 mm2 (+435%). Biliary stenoses were found in 4 cases (two arterial occlusions, one portal occlusion, and one associated occlusion). One case of partial portal vein thrombosis was found in one case of portal occlusion and resolved at 2 weeks. Ischemic damages adjacent to RF lesions were found in cases of combined occlusions. The reduction of liver perfusion increases significantly the size of RF lesions but is associated with a risk of biliary, portal, or parenchymal complications.