Duodenal perforation is rare and associated with a high mortality. Therapeutic strategies to address duodenal perforation include conservative, surgical, and endoscopic measures. Surgery remains the gold standard. However, endoscopic management is gaining ground mostly with the use of over-the-scope clips and vacuum-sponge therapy. A 67-year-old male patient was admitted to the emergency room for persistent epigastric pain, melena, and signs of sepsis. The physical assessment revealed reduced bowel sounds, involuntary guarding, and rebound tenderness in the upper abdominal quadrant. A contrast-enhanced computed tomography (CT) scan confirmed the suspicion of ulcer perforation. The initial laparoscopic surgical approach required conversion to laparotomy with overstitching of the perforation. In the postoperative course, the patient developed signs of increased inflammation and dyspnea. A CT scan and an endoscopy revealed a postoperative leakage and pneumonia. We placed an endoscopic duodenal intraluminal vacuum-sponge therapy with endoscopic negative pressure for 21 days. The leakage healed and the patient was discharged. Most experience in endoscopic vacuum-sponge therapy for gastrointestinal perforations has been gained in the area of esophageal and rectal transmural defects, whereas only few reports have described its use in duodenal perforations. In our case, the need for further surgical management could be avoided in a patient with multiple comorbidities and a reduced clinical status. Moreover, the pull-through technique via PEG for sponge placement reduces the intraluminal distance of the Eso-Sponge tube by shortcutting the length of the esophagus, thus decreasing the risk of dislocation and increasing the chance of successful treatment.