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Background Mediastinal abscesses after esophageal perforation or postoperative leakage nearly always require surgical intervention. Methods Patients with paraesophageal abscesses were treated with EUS-guided or endoscopic mediastinal puncture if the abscess was >2 cm and sepsis was present. Abscess cavities were entered with a 9.5-mm endoscope after balloon dilation to allow irrigation and drainage. Debris was removed with a Dormia basket. Concomitant pleural effusions were treated with transthoracic drains. Patients received intravenous antibiotics and enteral/parenteral nutrition. Results Twenty patients fulfilled the entry criteria. Simple drainage was sufficient in 4 cases, and puncture was impossible in one case. Of the 15 treated patients (age 39–76 years, 5 women) the etiology of perforation was Boerhaave's syndrome (n = 8), anastomotic leak (n = 3), and iatrogenic perforation (n = 4). Debridement was successful in all cases and required a median of 5 daily sessions (range 3-10). All patients became apyrexial, with a C-reactive protein < 5 mg/dL within a median of 4 days (range 2-8 days). Esophageal defects were closed with endoclips (n = 7), fibrin glue (n = 4), metal stents (n = 1), or spontaneously healed (n = 3). One patient died from a massive pulmonary embolism one day after successful debridement (mortality 7%). No other complications were seen. Median follow-up was 12 months (range 3-40 months). Conclusions Nonoperative endoscopic transesophageal debridement of mediastinal abscesses appears safe and effective.