Background: The aim of the study was to investigate the safety and the efficacy of the continuous infusion of bupivacaine and fentanyl through a preperitoneal catheter after midline laparotomy opioids are often used to decrease pain following laparotomy but are associated with unwanted side-effects. The effectiveness of local perfusion of bupivacaine 0.125 percent and fentanyl following midline laparotomy was studied. Methods: A prospective randomized study involving patients undergoing laparotomy for major abdominal surgery using a midline skin incision was undertaken. Patients were randomized to receive either intravenous morphine injection on demand with patient-controlled analgesia (M group) or continuous preperitoneal infusion of local bupivacaine 0.125 percent and fentanyl (P group).Results: Forty patients were recruited, 20 in each group. Patient demographics, surgical and recovery variables and complications were comparable in the two groups. The wound lengths were similar (median 14 cm in both groups). The postoperative pain scores at rest and with cough was higher in the preperitoneal group than that in the morphine group. The tidal volume was statistically higher in the preperitoneal group than the morphine group at T6, T12, and T24. There was no statistically significant difference in the postoperative sedation score in the both groups. There was a statistically significant decrease in sedation score in the preperitoneal group compared to the Morphine at 12 and 24h. There was a statistically significant decrease in mean arterial blood pressure starting from T3 till T 36 in the Preperitoneal group compared to the morphine group. There was a statistically significant decrease in sedation score in the preperitoneal group compared to the Morphine at 12 and 24h. In PONV there was no statistical significance between the two groups. There was a statistically significant decrease in the heart rate in the preperitoneal group more than the morphine group. Conclusion: Direct continuous local preperitoneal perfusion of bupivacaine 0.125 percent and fentanyl is as more effective than intravenous morphine for postoperative pain relief after midline laparotomy. It is a safe and feasible alternative to parenteral opioids.