Introduction: Endoscopic submucosal dissection (ESD) is the gold-standard treatment for superficial lesions of the digestive tract. No medico-economic study has been conducted in Europe. Material and methods: A monocentric study was conducted including all patients undergoing ESD between January 2015 and December 2017. The global cost of hospital stays was measured by microcosting, and revenue was based on the diagnosis-related group (DRG) system. The primary objective was to assess the cost/revenue balance. A medico-economic comparison with surgery was performed as a secondary outcome. Results: A total of 193 patients were prospectively included. The cost per procedure was E3463.79, subtracted from a E2726.84 revenue, with a deficit of ÀE736.96 per stay. Presence of comorbidities/complications increasing DRG value was the only predictive factor for a positive budgetary balance in a multivariate analysis (odds ratio 49.21, 95% confidence interval 11.3-214.25, p < 0.0001). In comparison with surgery, ESD was associated with shorter length of stay (11 vs 2 days; p < 0.0001) and lower morbidity (28% vs 14%; p ¼ 0.061), lower cost (E8960 vs E1770; p < 0.0001). Conclusion: The ESD cost/revenue balance is negative in 80% of cases. Given the benefits of ESD in terms of patient morbidity and financial savings compared with surgery, the implementation of a specific ESD reimbursement is warranted.