Objective <p>Comparison of traditional opioid-based analgesic protocols with multimodal pain management strategies in terms of postoperative pain, opioid consumption, and knee range of motion (ROM).</p> Materials and Methods <p>The study included 397 patients (mean age 67.4 ± 8.6&#xa0;years) undergoing unilateral TKA, divided according to the analgesic protocol: adductor canal block (ACB), periarticular local infiltration anesthesia (LIA), epidural analgesia, and traditional pharmacotherapy. Pain (VAS), opioid consumption (MME), and knee ROM were assessed over 4 postoperative days.</p> Results <p>Postoperative VAS scores differ significantly between cohorts at all time points (p &lt; 0.001). The ACB cohort had the lowest VAS scores on the day of surgery (3.30 ± 2.23) and on postoperative day 4 (2.10 ± 1.05), followed by the LIA cohort (2.30 ± 1.12). Epidural analgesia and traditional pharmacotherapy showed higher pain scores. Knee flexion on day 4 was highest in the ACB cohort (92.4° ± 7.2°), followed by the LIA cohort (88.5° ± 8.3°) (p &lt; 0.001). Opioid consumption was lowest in the ACB cohort (6.3 ± 5.8 MME) and highest in the traditional pharmacotherapy cohort (43.1 ± 12.8 MME) (p &lt; 0.001). BMI significantly influenced opioid consumption (p = 0.018), with higher BMI (&gt; 30&#xa0;kg/m²) which was associated with higher doses. However, BMI, age, and gender had no effect on knee ROM (p &gt; 0.05).</p> Conclusion <p>Multimodal protocols, including ACB in particular, improve pain control, reduce opioid consumption, and support faster rehabilitation.</p>