Introduction: Hysterectomy is a common procedure and postoperative pain is a considerable problem. Preemptive analgesia includes analgesic administration prior to surgical stimulus. Ketamine is a short acting anesthetic drug with analgesic and anti-inflammatory properties, reducing central sensitization of pain pathway and hyperalgesia. Objectives: This study aimed to assess the efficacy of preemptive use of ketamine as an analgesic drug, either by intravenous route or by subcutaneous infiltration at the incisional site, regarding perioperative hemodynamics, postoperative pain and gastrointestinal irritation symptoms. Patients and methods: 60 patients were enrolled in this study, divided into two equal groups (30 each) according to route of preemptive ketamine administration. Group (V) received 0.5 mg.kg^-1  intravenously while group (S) received 0.5 mg.kg^-1 subcutaneously at incisional site. Postoperative pain assessment for 24 H. using visual analogue score (VAS) was adapted as primary outcome objective, while secondary outcomes included hemodynamic parameter and postoperative nausea and vomiting (PONV). Results: Data were analysed. VAS score showed significant difference among studied groups in early 2 postoperative hours. VAS⁰ (V 2.40±0.62, S 1.96±0.92, P 0.038), VAS¹ (V 3.96±1.21, S 2.86±0.89, P 0.001), VAS² (V 4.00±0.94, S 3.33±0.88, P 0.007). Also, first time to pethidine intake (V 1.50±0.93 H, S 2.36±1.27 H, P 0.004). Other study objectives were comparable. Conclusion: Preemptive use of ketamine with subcutaneous infiltration at incisional site in total abdominal hysterectomy patients provided better analgesia in early postoperative hours rather than intravenous route with comparable hemodynamic parameter and side effects.