Background: Hepatic encephalopathy is a common complication of patients with hepatic cirrhosis and results in the alteration of mental status with a broad range of signs and symptoms based on its clinical severity. Lactulose or a nonabsorbable antibiotic are the mainstays of therapy for patients with persistent encephalopathy. Objective:  The aim of this study was to evaluate the efficacy of Polyethylene glycol (PEG) versus lactulose in management of hepatic encephalopathy. Patients and Methods: This study was carried out at Tropical Medicine Department (Al-Hussein and Sayed Galal University Hospitals). The study population included 100 patients who were diagnosed to have signs of the first to third degrees of  HE, during the period from January 2016 to August 2016.  The patients were divided and classified into two groups: Group I: Included 50 patients who had hepatic encephalopathy and were treated with lactulose, and Group II: Included 50 patients who had hepatic encephalopathy and were treated with 4 liters of PEG. Results: A total of 100  patients were randomized to each treatment arm.  Clinical efficacy was determined using HE index improvement. PEG was considered effective in 38 patients (76%) and lactulose in 40 patients (80.0%), which was not significantly different. Conclusions: PEG and lactulose decrease hepatic encephalopathy index with no statistically significant difference.