Background <p>Gastric endoscopic submucosal dissection (ESD) has been increasingly performed in elderly patients. However, bleeding remains a major complication. We aimed to comprehensively evaluate the risk factors of post-procedural bleeding, focusing on age and sex differences.</p> Methods <p>This was a nationwide, population-based, retrospective study utilizing the Korean NHIS database, comprising patients who underwent gastric ESD from November 2011 to December 2022. Operational definitions were created to identify the target population and post-procedural bleeding within 30&#xa0;days. Mixed-effect logistic regression models were used to identify risk factors for bleeding. The variables comprehensively included basic demographic factors, tumor characteristics, comorbidities, medication usage, and lifestyle behaviors.</p> Results <p>7825 bleeding events occurred in 164,968 procedures. In multiple logistic regression, significant risk factors included young age, male sex, higher Charlson Comorbidity Index (CCI), gastric cancer, multiple lesions, several comorbidities (highest aOR for renal failure undergoing hemodialysis) and antithrombotic agents (highest aOR for warfarin), underweight, current smoking, and heavy drinking. Being overweight and obese, however, showed a protective effect. Certain variables impacted bleeding risk differently based on age and sex. In the elderly group, high CCI and DOAC use were more influential, while male sex, smoking, and drinking had a diminished effect. Sex differences were more pronounced in the non-elderly group, with gastric cancer, warfarin use, and heavy drinking having a greater impact, while SES and obesity offered stronger protection in females.</p> Conclusions <p>This study identified risk factors for post-ESD bleeding and highlighted the role of age and sex in risk stratification and personalized treatment.</p>