During orthotopic liver transplantation (OLT), a marked decrease in blood pressure following unclamping of the portal vein and liver reperfusion is frequently observed and is termed postreperfusion syndrome (PRS). The predictive factors and clinical consequences of PRS are not fully understood. The goal of this study was to identify predictors of PRS and morbidity/mortality associated with its occurrence during OLT in patients with cirrhosis. During a 3-year period, all consecutive OLT procedures performed in patients with cirrhosis were studied. Exclusion criteria were OLT for acute liver failure, early retransplantation, combined liver/kidney transplantation, and living-donor related transplantation. PRS was defined as a decrease in the mean arterial pressure of more than 30% of the value observed in the anhepatic stage, for more than 1 minute during the first 5 minutes after reperfusion of the graft. Transplantation was performed with preservation of the inferior vena cava with or without temporary portocaval shunt. Associations between PRS and donor and recipient demographic data, recipient operative and postoperative outcomes were tested with bivariate statistics. Independent predictors of PRS were determined in multivariable logistic regression analysis. Of the 75 patients included in the study, 20 patients (25%) developed PRS. In a multivariable analysis, absence of a portocaval shunt [odds ratio (95% confidence interval) = 4.42 (1.18-17.6)] and duration of cold ischemia [odds ratio (95% confidence interval) = 1.34 (1.07-1.72)] were independent predictors of PRS. Patients who experienced PRS displayed more postoperative renal failure and lower early (<15 days after OLT) survival (80% versus 96%; P = 0.04). In conclusion, the absence of portocaval shunt and the duration of cold ischemia were independent predictors of intraoperative PRS. PRS was associated with significant adverse postoperative outcome. These results provide realistic clinical targets to improve patient outcome after OLT for cirrhosis. Liver Transpl 15:522–529, 2009. © 2009 AASLD.