OBJECTIVES: Hepatic encephalopathy (HE) is associated with high morbidity and mortality. Rifaximin-α is effective in reducing the recurrence of episodes of overt HE, and reduces hospital utilisation. The objective was to characterise the cost effectiveness of rifaximin-α plus a standard of care (SOC) versus SOC alone (lactulose) in patients with liver cirrhosis in Belgium.  METHODS: This economic evaluation used a Markov state transition model. The outcome metric was the incremental cost effectiveness ratio (ICER), derived from estimates of the cost/quality adjusted life years (QALYs). The payer perspective was that of the Belgian healthcare system. Outcome data were from two trials of rifaximin-α. Belgian costs data (2010) were derived from published sources. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. The time horizon was five years. Costs and benefits were discounted at 3% and 1.5%, respectively. Real world data were also applied into the model for length of hospital stay (LOHS) and number of admissions.   RESULTS: Average costs of the included elements of care were €31,262 in the rifaximin-α + SOC arm and €44,190 in the SOC arm, a difference of €12,927. The corresponding values for benefit were 2.5 and 1.9 QALYs per person, respectively, a difference of 0.6 QALYs over the five year period. This translated into a dominant base-case ICER at five years, ten years and for a lifetime simulation, meaning that compared to SOC, rifaximin-α + SOC improves quality of life and offers savings to the Belgian healthcare system. Key parameters impacting the ICER included LOHS and number of hospital admissions.  CONCLUSIONS: By reducing overt HE episodes, the likelihood of hospital admission and LOHS, rifaximin-α 550 mg + SOC in patients with recurrent HE in the context of liver cirrhosis, represented good value and was cost-saving compared with SOC.