INTRODUCTION: Post-sleeve gastrectomy (SG) proximal staple line leak is a rare yet serious complication. Endoscopic negative pressure therapy (ENPT) has emerged as a safe technique, showing promising results in treating leakages of the upper and lower gastrointestinal tract, often in conjunction with surgical interventions. A standardized treatment algorithm has not been established. This study aims to assess the safety and efficacy of ENPT in the multi-disciplinary management of proximal staple line leaks after SG. METHODS: This is an observational study of 40 post-SG proximal staple line leak cases treated with an ENPT-based approach. Revisional surgery was performed in addition to ENPT in critically ill patients or nondiagnostic imaging results. Success was defined as the healing of the defect and paraluminal cavity with no further need for surgical or endoscopic intervention following ENPT. RESULTS: Thirty-three patients were successfully treated with ENPT (82.5% success rate). Additional surgical interventions were performed in 37 patients, with re-laparoscopy, lavage, and drain of the abdominal cavity being the most frequently performed procedures. The mean duration of treatment was 25.6 days with an average of 6.4 endoscopic interventions per patient. CONCLUSIONS: ENPT is a safe and effective technique for treating proximal staple line leaks following SG. Its application should be considered alongside other endoscopic and surgical approaches.