Abstract Portal vein thrombosis may occur in cirrhosis; nevertheless, its prevalence, and predictors are still elusive. To investigate this issue, the Italian Society of Internal Medicine undertook the "Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry" (PRO-LIVER). This prospective multicenter study includes consecutive cirrhotic patients undergoing Doppler ultrasound examination of the portal area to evaluate the prevalence and incidence of portal vein thrombosis over a 2-year scheduled follow-up. Seven hundred and fifty-three (68 % men; 64 ± 12 years) patients were included in the present analysis. Fifty percent of the cases were cirrhotic outpatients. Viral (44 %) etiology was predominant. Around half of the patients had a mild-severity disease according to the Child-Pugh score; hepatocellular carcinoma was present in 20 %. The prevalence of ultrasound-detected portal vein thrombosis was 17 % (n = 126); it was asymptomatic in 43 % of the cases. Notably, more than half of the portal vein thrombosis patients (n = 81) were not treated with anticoagulant therapy. Logistic step-forward multivariate analysis demonstrated that previous portal vein thrombosis (p < 0.001), Child-Pugh Class B + C (p < 0.001), hepatocellular carcinoma (p = 0.01), previous upper gastrointestinal bleeding (p = 0.030) and older age (p = 0.012) were independently associated with portal vein thrombosis. Portal vein thrombosis is a frequent complication of cirrhosis, particularly in patients with moderate-severe liver failure. The apparent undertreatment of patients with portal vein thrombosis is a matter of concern and debate, which should be addressed by planning interventional trials especially with newer oral anticoagulants. Clinicaltrials.gov identifier NCT01470547.