Objective: To determine the frequency of efficacy of Rifaxamin in cases of hepatic encephalopathy. Methodology; This cross sectional study was carried out at Medical Department of Sheikh Zayed Hospital, Rahim Yar Khan during January 2017 to June 2017.The cases were selected irrespective of gender and age more than 25 years via non-probability consecutive sampling. The cases were categorized on the basis of laboratory and clinical data in two child pugh classes and the cases of child class B and C were selected. Hepatic encephalopathy was labelled on the basis of West Haven criteria. The cases of grade II or more were selected. These cases were offered Rifaxamin per oral in a dose of 550 mg thrice a day for 1 week and were looked daily for the absence of signs and symptoms of hepatic encephalopathy and was labelled as yes if all the signs and symptoms were absent. Results: In this study there were total 100 cases with mean age of 57.34±8.29 years. There were 68% males in this study and 36% had child pugh class B and 39% cases had hepatic encephalopathy grade IV. Efficacy of Rifaxamin was seen in 39% of the cases. Efficacy was significantly high in cases that had child class B where it was seen in 35 (54.68%) of the cases with p= 0.001. This efficacy was also significantly high in cases with grade IV of hepatic encephalopathy and was seen in 23 (58.97 %) of cases with p= 0.01. Conclusion: Rifaxamin is highly efficacious and it has shown significantly high in cases with child pugh class B and encephalopathy grade IV. Key words: Encephalopathy, Rifaxamin