The inflammatory reactions and tissue response after oesophagectomy are leading causes of postoperative morbidity and mortality. We evaluated the effects of intraoperative infusion of prostaglandin E1 (PGE1) on interleukin-6 (IL-6) levels, (A-a) DO2, pulmonary function and complications. This randomised double-blind clinical trial study was performed on patients undergoing transthoracic oesophagectomy due to cancer. Thirty patients were randomly allocated to two groups: the PGE1 group (infusion of PGE1, 20 ng.kg−1.min−1) and a placebo group (infusion of normal saline 0.9%). The infusion was started before induction of anaesthesia and continued until the end of the operation. The groups were comparable in basic characteristics and preoperative pulmonary function. Patients in the PGE1 group were discharged significantly earlier from the intensive care unit (72±9 vs 83±17 hours) and hospital (13±4 vs 18±8 days) (P=0.04 and 0.03, respectively). The (A-a) DO2 was significantly less in the PGE1 group at 12 and 24 hours after the operation (P=0.001, P=0.003, respectively). Postoperatively, IL-6 levels were significantly higher in the placebo group than in the PGE1 group. There were no differences in the forced expiratory volume in the first second or forced vital capacity. The findings indicate that infusion of PGE1 attenuates the increase in serum levels of IL-6 in patients undergoing esophagectomy and improves the (A-a) DO2. Stays in the intensive care unit and hospital were shorter in the PGE1 group. However, there were no differences in pulmonary complications.