The specific contribution of splenic blood inflow to portal hypertension in patients with cirrhosis is still unclear. In this study, we investigated this contribution by assessing the hemodynamic effects of transient splenic artery occlusion. In 15 cirrhotic patients, portal pressure gradient (PPG) was measured just before inserting a transjugular intrahepatic portosystemic shunt (TIPS), in baseline conditions, for 15 minutes after splenic artery occlusion and 5 minutes after recovery. Splenic artery occlusion caused a significant decrease in PPG (range, −4% to −38%, median −20%, P < 0.001) which promptly returned to baseline values after recovery of the splenic inflow. The decrease in PPG showed a significant correlation with spleen volume (r = 0.70, P < 0.005), liver volume (r = −0.63; P < 0.01), and spleen/liver volume ratio (r = 0.82, P < 0.001). Seven out of eight patients with a spleen/liver volume ratio greater than 0.5 had a marked decrease in PPG (>20%), whereas none of patients with a ratio lesser than 0.5 had a marked PPG response. In conclusion, in cirrhotic patients with portal hypertension, splenic artery occlusion causes a significant reduction in portal pressure (PPG). The drop in PPG is directly related to spleen volume and indirectly related to liver volume. The spleen/liver volume ratio accurately predicts the drop in PPG and may be used to identify patients who could obtain a significant advantage from surgical and nonsurgical procedures decreasing splenic inflow. Liver Transpl 12:1237-1243, 2006. © 2006 AASLD.