ABSTRACT Background and study aims: To assess the cost-effectiveness of introducing endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection in selected patients into the standard of care of Barrett's esophagus patients with high-grade dysplasia or low-grade dysplasia in Spain. Methods: The disease evolution was modeled via a semi-Markov model. The treatment strategies compared included endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection and the Standard of Care (esophagectomy or palliative chemoradiotherapy according to disease status for high-grade dysplasia and endoscopic surveillance for low-grade dysplasia). Efficacy rates, transition probabilities and utility values were obtained from the literature. Clinical management patterns and resource use were modeled according to Spanish clinical expert opinion. Costs were expressed in euros (€) from 2016 reflecting the Spanish National Health System perspective. Sensitivity analyses were performed to assess the robustness of the model. Results: With respect to the Spanish Standard of Care, endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection was a dominant strategy for high-grade dysplasia patients. When a willingness-to-pay threshold of €30,000 per quality-adjusted life-years gained was considered, this was cost-effective for low-grade dysplasia patients (€12,865 per quality-adjusted life-years gained). The sensitivity analyses supported the base case analysis results and pointed towards the main drivers of uncertainty in the model. Conclusions: From a health care decision-maker, endoscopic treatment based on radiofrequency ablation plus endoscopic mucosal resection is the intervention of choice for dysplasic Barrett's esophagus patients in Spain.