Objective: Surgical-site infiltration with local anesthetics is a key component of multimodal analgesia regimen for adequate postoperative pain management. This randomized, double-blind study was designed to evaluate the local analgesic efficacy of pethidine in patients undergoing total abdominal hysterectomy (TAH) through a Pfannenstiel incision. Materials and Methods: Patients were randomized into two groups. The first group received wound infiltration (WI) with 0.5 mg/kg pethidine, diluted in 15 ml normal saline, and injected in the fascial layer at the end of surgery, combined with a simultaneous intramuscular (IM) injection of 2.5 ml normal saline (WI group). The second group received WI with 15 ml normal saline combined with an IM injection of 0.5 mg/kg pethidine and diluted in 2.5 ml normal saline (IM group). All patients received general anesthesia following a standardized anesthetic protocol. Study end points were 24-h total morphine consumption and pain scores based on a visual analog scale (VAS) at rest and on coughing at 1, 3, 6, and 24 postoperative h, as well as sedation scores observed using a 0–10 numeric rating scale. Adverse effects from morphine uptake, such as nausea, vomiting, and the need for rescue antiemetics, were recorded as well. Results: Postoperative VAS assessments showed no statistically significant advantage between WI and IM method, while the total (24h) consumption of morphine was lower in the IM, compared to the WI group (27.2%). The latter demonstrated a consistently higher median sedation score at all assessed time points after the operation (P < 0.05); however, it was significantly different only at the 6 h time point. Conclusions: Local WI with pethidine after TAH did not reduce the total morphine consumption for the first 24 h postoperatively. Morphine consumption was lower in the IM group, compared to the WI group. Further studies are needed to assess the effectiveness of pethidine as a local anesthetic agent.