Abstract Background: Peptic ulcer perforation is a common life-threatening surgical emergency. Graham omental patch is performed for plugging of perforated peptic ulcer. Many endoscopic methods have been used to treat acute perforated peptic ulcer such as over the scope clips, standard endoscopic clips, endoscopic sewing and metallic stents. The main idea in endoscopic management of acute perforated peptic ulcer is early decontamination and decrease sepsis by interventional radiologic drainage. Methods: This is a prospective randomized controlled clinical trial. This study included patients who were developed acute perforated peptic ulcer manifestations and were admitted to our hospital between December 2019 and August 2021. Sample size was 100 patients divided into 2 equal groups. Endoscopic group (EG): included 50 patients who were subjected to endoscopic management. Surgical group (SG): included 50 patients who were subjected to surgical management. Results: One hundred patients were randomized into 2 groups: SG (50) and EG (50). Median age of patients was 36 (range 27:54) and 47 (range 41:50) years-old in SG and EG, respectively. Males constituted 72% and 66% in SG and EG, respectively. Median length of postoperative hospital stay was 1 (range: 1–2) days in EG, while in SG was 7 (range 6–8) days. Postoperative complications in SG patients were 58% in form of fever, pneumonia, leak, abdominal abscess, renal failure and incisional hernia (11%, 5%, 5%, 3%, 2% and 3%, respectively). Postoperative complications in EG patients were 24% in form of fever, pneumonia, leak, abdominal abscess, renal failure and incisional hernia (10%, 0%, 2%, 0%, 0% and 0%, respectively). Conclusion: Combined endoscopic and interventional radiological drainage can effectively manage acute perforated peptic ulcer without the need for general anesthesia, with short operative time, in high risk surgical patients with low incidence of morbidity & mortality.