<b><i>Background and Aim:</i></b> Liver cirrhosis is characterized by high morbidity and mortality rates. This study was addressed to evaluate the epidemiological and economic impact of cirrhosis on hospitalizations in a large population in Italy. <b><i>Methods:</i></b> Epidemiological analysis was performed using hospital discharge sheets of 57,720 hospitalizations due to liver disease from 2006 to 2008, selected from the Veneto regional archive. In a sample of 100 randomly selected hospitalizations, a detailed cost analysis was performed and a comparison was made with sets of patients admitted for heart failure (HF) and chronic obstructive pulmonary disease (COPD). <b><i>Results:</i></b> Among patients with cirrhosis, ascites emerged as the most frequent cause of admission, followed by hepatic encephalopathy, hepatocellular carcinoma, and upper gastrointestinal bleeding. Encephalopathy and ascites were the complications with the highest rates of readmission. The detailed cost analysis of hospitalizations revealed that economic expenses in the set of patients admitted for cirrhosis were about 30% higher than those for patients admitted for HF or COPD, mainly due to the longer duration of hospitalization. <b><i>Conclusions:</i></b> Cirrhosis has a relevant epidemiological and economic impact on hospitalizations and preventive strategies for its clinical management are warranted.