Objective & methodology: The objective of this study was to determine the efficacy of rifaximin in cases of chronic liver disease presenting with hepatic encephalopathy. In this descriptive cases series study, which was conducted at Sir Ganga Ram Hospital Lahore, Sharif Medical City Lahore and DHQ hospital, Gujranwala from May 2018 to December 2018. The cases of both genders with age range of 30–70 years having CLD (Child Pugh Class B & C) and acute hepatic encephalopathy of grade II or more irrespective of the cause were included in this study. The cases with other co morbid conditions like DM, HTN, renal or cardiac failure and those taking sedative were excluded from this study. Hepatic encephalopathy was labeled according to the West Haven Criteria. The cases of HE were given Rifaximin in a dose of 550 mg tds for 7 days and complete resolution of hepatic encephalopathy at 7th day was labeled as positive efficacy. Results: In this study there were total 150 cases out of which 85 (56.67%) were males and 65 (43.33%) females. The mean age was 55.34±5.12 years. There were 75 cases in each child pugh class B and C and 57 (38%) cases had grade IV hepatic encephalopathy. Efficacy of rifaximin was seen in 82 (45.33%) cases. The efficacy was significantly high in cases that had Child Pugh Class B where it was seen in 52 (69.33%) cases as compared to 40% in class C (p=0.03). Efficacy was also significantly better in grade III encephalopathy affecting 35 (72.91%) cases in contrast to 17 (29.82%) cases with grade IV in their respective group with p= 0.001. Conclusion: Rifaximin is good antibiotic for gut flora but it relieves HE in only half of cases. It is significantly better in cases with Child pugh class B and with encephalopathy grade III. Key words: HE, CLD, Rifaximin, West Haven Criteria