Background: Postoperative pain after cardiothoracic surgery is one of the most severe types of postoperative pain due to sternotomy or muscle-dividing incision of the chest wall. It leads to inability to cough and to maintain their functional residual capacity which leads to retention of secretion and pneumonia. So, proper control of post-operative pain improves the patient's outcome. Objective: The present study was designed to evaluate the quality and efficacy of post-operative analgesia of clonidine and/or magnesium sulphate when added to bupivacaine and morphine in thoracic epidural analgesia for cardiac surgery. Patients and methods: A prospective, double blind randomized study was carried out on eighty patients classified into four equal groups, i.e. group I (control): received 5 ml bupivacaine (0.5%) + 2mg morphine sulphate (to be diluted to 10 ml of 0.9% saline), group II: received the same solution for group I + 50 mg of magnesium sulphate, group III: received the same solution for group I + 75 μg clonidine and group IV: received the same solution for group I + 50 mg magnesium sulphate and 75 μg clonidine. All patients received the first postoperative analgesic dose through the epidural catheter just after being transferred to postoperative intensive care unit (ICU). According to the scheduled intervals, heart rate, mean arterial blood pressure, arterial blood gases, as well as visual analuge score (VAS) were recorded for 24 hours postoperatively. Duration of analgesia, frequency of top up analgesic doses and surgical stress response parameters (serum blood glucose and cortisol) were also recorded. Results: Groups III and IV recorded prolonged duration of analgesia, decreased requirements of bupivacaine and morphine, with improvement of pain relief. All results of group III indicated that clonidine was more effective than magnesium sulphate when used as adjuvant for epidural analgesia for postoperative pain management. Conclusion: Epidural clonidine prolonged the duration of analgesia, decreased the local anesthetic requirement and improved quality of pain relief, when added to bupivacaine and morphine for postoperative analgesia after cardiac surgery when compared to magnesium sulphate that had no beneficial effect as an adjuvant.