OBJECTIVES: Transjugular Intrahepatic Portosystemic Shunt (TIPS) is considered as rescue therapy following the failure of endoscopic procedures to manage recurrent bleeding in patients with portal hypertension. Trials have shown clinical benefit, from the earlier use of TIPS with ePTFE covered stent-grafts in patients with persistent bleeding at high risk for treatment failure and death. A cost-effectiveness analysis of the early use of TIPS with ePTFE covered stent-grafts compared to the endoscopic approach has been developed. METHODS: A 2-years Markov model was adapted considering the Spanish National Healthcare System perspective in order to measure the clinical and economic consequences of early TIPS with ePTFE covered stent-grafts, compared to endoscopic band ligation EBL plus pharmaceuticals in high risk patients with acute variceal bleeding. Clinical management patterns and resource consumption were defined by an interview process with Spanish key opinion leaders. The model was populated with published clinical data including an RCT. Healthcare costs were obtained from Spanish databases and expressed in €2015.Univariate sensitivity analyses were performed to test the model’s robustness. RESULTS:  Over 2-years, the economic model shows a minimal incremental cost per patient of €57 using early TIPS with ePTFE covered stent-grafts €7,657 compared to endoscopic approach €7,600. Although TIPS implant and subsequent re-interventions produced a reduced incremental cost, main cost savings came from fewer recurrent bleeding and related EBL procedures. Mortality was reduced in the early TIPS alternative by 56% compared to endoscopic treatment, resulting in 0.4 life-years gained (LYG) per patient. Consequently, incremental cost per LYG ratio resulted in €137. Sensitivity analysis indicated that model estimations were maintained across the scenarios tested. CONCLUSIONS: Early TIPS with ePTFE covered stent-grafts compared to endoscopic band ligation plus pharmaceuticals in high risk patients with acute variceal bleeding would improve survival at a neutral incremental cost for the Spanish NHS.