Controversies exist about the management of esophageal perforation in order to eliminate the septic focus. The aim of this study was to assess the etiology, management, and outcome of esophageal perforation over a 12-year period, in order to characterize optimal treatment options in this severe disease. Between May 1996 and May 2008, 44 patients (30 men, 14 women; median age 67 years) with esophageal perforation were treated in our department. Etiology, diagnostic procedures, time interval between clinical presentation and treatment, therapeutic management, and outcome were analyzed retro- or prospectively for each patient. Iatrogenic injury was the most frequent cause of esophageal perforation (n= 28), followed by spontaneous (n= 9) and traumatic (n= 4) esophageal rupture (in three patients, the reasons were not determinable). Eight patients (18%) underwent conservative treatment with cessation of oral intake, antibiotics, and parenteral nutrition. Twelve (27%) patients received an endoscopic stent implantation. Surgical therapy was performed in 24 (55%) patients with suturing of the lesion in nine patients, esophagectomy with delayed reconstruction in 14 patients, and resection of the distal esophagus and gastrectomy in one patient. In case of iatrogenic perforation, conservative or interventional therapy was performed each in 50% of the patients; 89% of the patients with a Boerhaave syndrome underwent surgery. The hospital mortality rate was 6.8% (3 of 44 patients): one patient with an iatrogenic perforation after conservative treatment, and two patients after surgery (one with Boerhaave syndrome, one with iatrogenic rupture). No death occurred in the 25 patients with a diagnostic interval less than 24 hours, whereas the mortality rate in the group (n= 16 patients) with a diagnostic interval of more than 24 hours was 19% (P= 0.053). In three patients, the diagnostic interval was not determinable retrospectively. An individualized therapy depending on etiology, diagnostic delay, and septic status leads to a low mortality of esophageal perforation.