A prolongation of QT interval has been shown in patients with cirrhosis and it is considered as part of the definition of the so-called 'cirrhotic cardiomyopathy'. The aim of the present study was to assess the determinants of QT interval prolongation in cirrhotic patients. Forty-eight male patients with different stages of liver disease were divided into three subgroups according to the Child-Pugh classification. All patients underwent a 24-h ECG Holter recording. The 24-h mean of QT intervals corrected for heart rate (termed QTc) and the slope of the regression line QT/RR were calculated. HRV (heart rate variability), plasma calcium and potassium concentration and HVPG (hepatic venous pressure gradient) were measured. QTc was progressively prolonged from Child A to Child C patients (P=0.001). A significant correlation between QTc and HVPG was found (P=0.003). Patients with alcohol-related cirrhosis presented QTc prolongation more frequently than patients with post-viral cirrhosis (P<0.001). The QT/RR slope was steeper in subjects with alcoholic aetiology as compared with viral aetiology (P=0.02), suggesting that these patients have a further QTc prolongation when heart rate decreases. The plasma calcium concentration was inversely correlated with QTc (P<0.001). The presence of severe portal hypertension was associated with decreased HRV (P<0.001). Cirrhotic patients with a more severe disease, especially of alcoholic aetiology, who have greater HVPG and lower calcium plasma levels, have an altered ventricular repolarization and a reduced vagal activity to the heart, which may predispose to life-threatening arrhythmias.