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Background: Endoscopic submucosal dissection (ESD) is a standard treatment option for early gastric cancer (EGC) in Asia; however, data about ESD efficacy in Western populations are limited. Furthermore, outcomes of EGC treatment after ESD or surgery have not been compared in Western cohorts. This study aimed to compare short-term and long-term results of ESD and surgery for EGC.Methods: This retrospective case-control study included patients with EGC treated in two largest cancer centers in Eastern Lithuania between 2005 and 2016. Propensity score nearest-neighbor 1:1 matching, based on clinicopathologic characteristics, was performed between patients who underwent ESD and surgery. The primary endpoint of the study was 5-year disease-free survival (DFS).Results: Of 260 eligible patients, 42 (16.1%) underwent ESD. After matching, two well-balanced groups consisting of 42 patients in each were analyzed. The operation time (83 vs. 151 min., p = 0.001) and postoperative hospitalization stay (5.4 vs. 13.4 days, p = 0.001) was significantly shorter in the ESD group. 5-year DFS rate was significantly higher in the surgery group (97.6% vs. 77.5%, p = 0.002). However, this difference was reduced after exclusion of non-curative ESD cases (97.6% vs. 89.7%, p = 0.099). There was no significant difference in 5-year OS rate between the study groups (73.8% vs. 69.0%, p = 0.599).Conclusions: ESD might be an excellent alternative to surgery for EGC if curative resection is achieved. Non-curative ESD is associated with poor DFS and high rate of recurrence. Additional surgery should be recommended after non-curative ESD whenever treatment-associated risk is acceptable. [ABSTRACT FROM AUTHOR]