Background: Intravenous patient-controlled analgesia (IV-PCA) with morphine is commonly used for postoperative pain control following major abdominal surgery. However, large amounts of morphine may lead to significant adverse events. Multimodal analgesia using a non-opioid analgesic, in addition to an opioid analgesic, has been suggested as a way to improve postoperative pain control and to reduce opioid use. Objective: To compare the difference between intravenous Ketamine or Magnesium Sulfate or both on postoperative morphine consumption after major abdominal surgery. Patients and Methods: This study included 100 patients of both sexes admitted for major abdominal surgery. They were randomly allocated into four equal groups. Group I: Control group, Group II  received only ketamine, Group III  received only magnesium sulfate and Group IV  received both ketamine and magnesium sulfate. The following parameters were assessed in the four groups: Heart rate (HR), blood pressure (BP), respiratory rate (RR), end tidal Co2, the severity of pain on modified Ramsay sedation scale, time to first request for analgesia postoperatively, the number of rescue analgesia given, , adverse events, the level of the patient satisfaction and total dose of morphine consumption postoperatively (mg/48h). Results: This study showed that the hemodynamics of the patients were more stable in (ketamine + magnesium sulfate) and ketamine only group than in magnesium sulfate only group and control group throughout all 48 hours postoperative. Usage of ketamine decreases postoperative pain and analgesic consumption in the first 48 hours after surgery along with longer pain free period compared to patients who were given magnesium sulfate only and control group. Ketamine is highly effective in postoperative pain control in major abdominal surgery without any hazards on patients. The total consumption of morphine, and additional analgesic requirements were less, while the satisfaction level of patients were higher in (ketamine+ magnesium sulfate) and ketamine only group. Conclusion: Ketamine is one of the most advantageous adjuvant drugs for treating postoperative pain, while magnesium sulfate alone is less effective, with increase in opioid side effect. Combination of ketamine+ magnesium sulfate is better in treating postoperative pain and preserve patient hemodynamics with decrease in opioid side effect.