Postoperative air leaks associated with residual pleural space is a well known complication contributing to prolong hospitalization. Many techniques have been proposed for the treatment of this complication. Between 1999 and 2009, 39 patients with air leaks associated with residual pleural space (>3 cm at chest X-ray) persisting over three days after major lung resection were enrolled in this study. All patients were treated with combined pneumoperitoneum and autologus blood patch. Pneumoperitoneum is obtained by the injection of 30 ml/kg of air under the diaphragm, using a Verres needle through the periumbilical area. The blood patch is obtained by instillating 100 ml of autologus blood through the chest tubes. No patients experienced complications related to the procedure. Obliteration of pleural space was obtained in all the patients at a maximum of 96 h postoperatively. Air leaks stopped in all the cases at a maximum of 144 h from surgery. Chest tube was removed 24 h after the air leakage disappearance. Our 10-year experience supports the early, combined use of pneumoperitoneum and blood patch whenever pleural space and air leaks present after major pulmonary resection. This approach may be recommended because of its easiness, safety, effectiveness, and the low costs.