Simple SummaryEndoscopic submucosal dissection (ESD) for early gastric cancer patients using antithrombotic agents (ATA) is becoming more common than ever before due to the aging of society and rising ATA prescription rates. The relationship between perioperative ATA use and post-ESD bleeding is still debatable at this time. Furthermore, it is uncertain whether the suggested duration of ATA cessation in current guidelines is sufficient to normalize the bleeding risk. This study examined the effects of ATA on post-ESD bleeding through propensity score-matching analysis between ATA users and non-users. We discovered that ATA use was independently associated with a higher incidence of post-ESD bleeding. This tendency was significantly observed in patients who either continued or insufficiently discontinued ATA and those who sufficiently discontinued ATA, according to current guidelines. Given these findings, we suggest careful observation after ESD for patients using ATA, regardless of their cessation status.AbstractWhether antithrombotic agent (ATA) usage increases the risk of gastric post-endoscopic submucosal dissection (ESD) bleeding remains controversial. The aim of this study was to elucidate the effects of usage, type, and cessation timing of ATA on post-ESD bleeding. A total of 4775 early gastric cancer patients undergoing ESD were analyzed; 1:3 propensity score matching between ATA and non-ATA groups resulted in 318 and 767 matched patients in each group, respectively. Outcomes were compared between the two groups using a generalized estimating equation method. After matching, post-ESD bleeding rates in ATA users and non-users were 9.1% and 4.2%, respectively (p= 0.001). In multivariable analysis, ATA usage was independently associated with an increased risk of post-ESD bleeding (adjusted odds ratio: 2.28, 95% confidence interval: 1.34–3.86). Both the continued or insufficient cessation groups and the sufficient cessation group had an increased incidence of post-ESD bleeding compared to their matched controls (12.5% versus 5.2%,p= 0.048; 8.1% versus 3.9%,p= 0.014). Post-ESD bleeding rates in antiplatelet agent users were significantly higher than those of their matched controls (8.3% versus 4.2%,p= 0.010). ATA usage increased the risk of post-ESD bleeding even after its sufficient cessation. Careful observation after ESD is required regardless of the cessation status of ATA.