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Background: Hepatic encephalopathy is an important evidence that confirms impairment of liver function, may occur in about 40% of cirrhotics. Data about efficacy of rifaximin plus lactulose in the treatment of Vietnamese patients was still limited. This study aimed to determine the precipitating factors and to access the efficacy of lactulose plus rifaximin in overt hepatic encephalopathy. Patients and Methods: The prospective single-blind randomized controlled trial, 43 cirrhotics with overt hepatic encephalopathy without portal systemic shunting addmitted to gastroenterology department of Cho Ray Hospital from March 2019 to August 2019, were randomized into two groups (group A lactulose plus rifaximin 1.100 mg/day, n = 21; and group B only lactulose; n = 22). All patients were recorded for onset factors, clinical characteristics and assessing the recovery of hepatic encephalopathy. Results: The mean age of patients in this study was 54.8 ± 12.1 years (the ratio of male to female patients is 4.38 : 1). The leading cause of cirrhosis was alcohol (39.5%). The most common clinical symptoms were jaundice (83.7%), spider naevi (41.9%) and ascites (37.2%). The most common triggers were infection (51.2%), gastrointestinal bleeding (37.2%) and constipation (25.6%). The percentage of patients with complete improvement after treatment with lactulose plus rifaximin was 81% compared to 63.6% in the lactulose-treated patients only (95% CI: 0.539 - 1.147, p value = 0.206). Conclusion: Our data revealed that common triggers of hepatic encephalopathy were infections, gastrointestinal bleeding and constipation. The combination of lactulose plus rifaximin was more effective than rifaximin alone in the treatment of overt hepatic encephalopathy. Key words: hepatic encephalopathy, precipitating factor, lactulose, rifaximin