One hundred patients undergoing primary unilateral TKA were randomized to receive an adductor canal block (ACB) either 30 minutes before general anesthesia (n=50) or postoperatively in the post-anesthesia care unit (n=50). All patients also received periarticular local infiltration analgesia. The primary outcome was postoperative morphine consumption as rescue analgesia within 24 hours and during the entire hospitalization. Secondary outcomes included time to first rescue analgesia, intraoperative and postoperative stress responses (cortisol and ACTH levels), postoperative pain, range of knee motion, ambulation distance, time to discharge, chronic pain incidence, and complications. Outcomes were assessed up to 3 months postoperatively. Overall, the study revealed that preoperative ACB significantly reduced morphine consumption, stress markers, pain scores, and the incidence of chronic pain compared to postoperative ACB. These findings suggest that a preoperative ACB provides better pain control, mitigates stress responses, and may lower chronic pain risk in patients undergoing TKA.