OBJECTIVES: This study was performed to assess the French annual economic burden of hospitalizations for Hepatic Encephalopathy (HE). Social security payer perspective was chosen using PMSI Database 2012 and 2013 (exhaustive French health claims database). Discriminatory factor of EH hospitalization costs were analyzed by studying patients’ characteristics. METHODS: A retrospective cohort was performed from national PMSI database 2012 and 2013. Log-linear regression was done to model EH hospitalization costs per patient by exploring variables. RESULTS: The study collected more than 5,000 patients hospitalized for EH (7,000 stays) annually in 2012 and 2013. Annual economic burden of EH hospitalizations amounted to €40 million. More than 70% of these annual cost was accounted by 47% of patients with a level 3 or 4 severity DRG (Diagnosis Related Group). Patients with a level 4 severity DRG induced 33% of costs (€13 million in 2012 and €14 million in 2013). A log linear model was performed on 5,267 patients hospitalized in 2012 and followed one year: it explained 78% of hospitalization costs. Age had a concave effect with costs increasing until a 50 years threshold. Beyond this threshold, age had a negative effect on costs. Gender had no impact on costs of support stays. Hospitalization of patient with a renal insufficiency increased costs of 11%, 6.8% with a bacterial infection, 8.1% with a respiratory disease and 7.5% with a malnutrition. Finally costs increased with of 1.2% for each supplementary day, 3.4% for each passage in intensive care unit and 0.7% for death. CONCLUSIONS: More than 40 million euros are spent per year by Social Security in France for HE hospitalizations with a mean cost of € 5,535 (±SD €6,411). HE patients with a level 4 severity DRG represent 33% of total cost.