Background: Hepatitis E virus (HEV) infection is enterically transmitted and usually present as acute self limiting infection. However, in cirrhotic patients, it is usually problematic being a possible trigger of decompensation with high mortality rates. Objectives: To determine the seroprevalence of HEV IgG and risk factors of HEV exposure in cirrhotic patients. Also, to determine the role of acute HEV infection as a possible trigger of acute-on-chronic liver failure (ACLF) in cirrhotic Egyptian patients in East Delta and to compare different clinical, laboratory and ultrasonographic features between acute HEV positive and negative ACLF patients. Methods: Two groups of cirrhotic patients were enrolled; group (1) included 216 patients with compensated cirrhosis and group (2) included 67 cirrhotic patients presenting with ACLF. For group (1) patients; HEV seroprevalence was determined by testing for anti-HEV IgG by ELISA, while acute HEV infection was detected in group (2) patients by testing for anti-HEV IgM and HEV RNA by ELISA and RT-PCR respectively. For ACLF cases, full history, clinical, laboratory and ultrasonographic findings were recorded. Results: The seroprevalence of anti-HEV IgG was 39.4 % in cirrhotic patients and well water use was the only significant predictor affecting HEV seropositivity. Acute HEV infection was detected in 13.4% (9/67) of cirrhotic patients with ACLF. It came third among the identified triggering factors of ACLF following bacterial infections (22.4%) and variceal bleeding (14.9%). Acute HEV positive ACLF patients showed significantly higher levels of liver enzymes than acute HEV negative cases. Conclusion: In our locality, securing a safe water supply seems to be the most important HEV preventive measure. Meanwhile, clinicians should consider testing for acute HEV infection in cirrhotic patients developing ACLF, particularly those showing marked liver enzyme elevation.