Abstract INTRODUCTION: No unique technique has proved efficient enough in controlling post cardiothoracic surgery pain. A variety of agents and techniques have been used to control pain following cardiothoracic surgery; interpleural regional analgesia is one such technique. OBJECTIVE: There are many nerve endings in the pleural cavity. The local anesthetic action of meperidine administered interpleurally was evaluated in this study. METHODS: In a double blind clinical trial, 90 patients undergoing coronary artery bypass graft surgery were randomized into four groups as intravenous meperidine (G1), interpleural meperidine (G2), interpleural meperidine and bupivacaine (G3) and interpleural bupivacaine (G4) groups. At the end of surgery, interpleural catheter was placed in all groups and the medication was prescribed. In the cardiac intensive care unit, narcotic requirements and pain scores were registered. Collected data were analyzed by appropriate tests including t-test and chi-square test. P values below 0.05 were considered as significant. RESULTS: There were no significant differences in age, weight, sex and ASA (American Society of Anesthesiologists) class between the four groups. At all time periods, the pain levels measured by the visual analogue score (VAS) were significantly lower in the G3 and G4 groups (P<0.05). The total narcotic requirements in the first 24 hours of postoperative period were significantly lower in the G3 and G4 groups (P<0.05). CONCLUSION: In spite of analgesic effects of subarachnoid meperidine, intraarticular morphine and interpleural bupivacaine, interpleural meperidine does not change pain scores or narcotic requirements postoperatively. Keywords: Meperidine, bupivacaine, postoperative, pain, thoracic surgery, cardiac surgical procedure..