Dehiscence of upper gastrointestinal sutures still remains a severe clinical problem and often requires complex surgical repair. Despite its multifactorial aetiopathogenesis, endoluminal pressure seems to play an important role in the onset and maintenance of this complication. The efficacy of isoperistaltic endoluminal drainage (IED) in the operative treatment or prevention of upper gastrointestinal surgical dehiscence was assessed in a retrospective study. The IED procedure is obtained by means of a two-way nasogastric tube inserted in the proximal jejunum through the abdominal and advanced to the site of the leak in order to achieve low endovisceral pressure, normal intestinal free flow downstream of the lesion and monitoring of the healing process. Over the past decade 31 patients (mean age 62 years; 52.9% male) with postoperative dehiscences of the thoraco-abdominal oesophagus, stomach or duodenum underwent reintervention. During the surgical repair an IED was inserted in 17, while no IED was inserted in 14 (NOIED): the two groups were well matched for age, gender, primary pathology, site and type of leak. The overall operative mortality (30 days) was 16% (12.5% IED vs. 20% NOIED), and morbidity was 45% (37.5% IED vs. 53.3% NOIED). The rate of leak relapse was significantly different: 6% IED vs. 20% NOIED. In the last 5 years the IED procedure has also been used preventively with promising outcomes in another 16 other high-risk upper gastrointestinal suture patients. The results of this retrospective study appear to support the use of the IED procedure to minimize the risk of failure of the suture/anastomosis in upper gastrointestinal surgery. Other studies are needed to validate the efficacy of this supplementation of surgical treatment.