Background: besides an opioid analgesic, multimodal analgesia using a non-opioid analgesic, in atrial to decrease opioid use and to increase postoperative pain control. Objectives: To compare the effect of intra-operative infusion of ketamine and magnesium sulphate in open gynaecological surgeries on post-operative pain, total morphine consumption, post-operative nausea, and vomiting in Qena University Hospitals. Patients and methods: A prospective study. Conducted in Qena University Hospital, South Valley University, Qena, Egypt. The study was conducted on fifty patients (ASA I or II) scheduled for open gynaecological surgeries under general anaesthesia: group A: Ketamine (0.2 mg/ kg) bolus than the continuous supply of ketamine (0.05 mg/kg/h), group B: Magnesium sulphate (50mg/ kg) bolus and followed by continuous infusion of magnesium sulfate(10mg/kg /h). Results:  the visual analogue scale was found to be significantly higher in group B compared to group A in 2, 4, and 8 hrs time intervals. The mean opioid (Morphine/Pethidine) consumption doses over 24h were lower in group A compared to group B. There is no significant difference regarding adverse events between the two studied groups. Conclusion: Intraoperative magnesium sulfate and ketamine infusion in patients exposed to gynecological surgeries with general anesthesia could and decreased the post-operative opioid requirement. Ketamine showed a significant preemptive analgesic effect compared to MgSO4 at 2 and 8 h postoperatively. VAS was significantly lowered in Ketamine than MgSO4.