PURPOSE: The study aimed to evaluate efficacy of an intraoperative periarticular injection (PAI) in improving postoperative outcomes, including pain relief and reducing opioid consumption in patients undergoing arthroscopic anterior cruciate ligament reconstruction (aACLR) with hamstring tendon autograft. METHODS: This prospective, assessor-blinded, two-surgeon clinical trial was conducted from. March 20 RESULTS: 142 patients in the PAI group and 146 patients in the nPAI group were analyzed. In the PAI group, a lower VAS score at immediate postoperative period and postoperative 4-hour and 24-hour 24 was observed compared with the nPAI group. Proportions of patients achieving MCID were higher in the PAI group at all time points compared to nPAI. Cumulative morphine consumption was significantly reduced in the PAI group (p<
0.001). CONCLUSIONS: PAI during aACLR with hamstring autograft significantly improved pain scores and reduced opioid consumption compared to nPAI. While statistical differences were found, cohort-specific MCID analysis showed a clinically relevant benefit at 24 hours, with 54.2% of the PAI group achieving meaningful pain relief versus 23.3% in the nPAI group. These results suggest that PAI offers time-dependent, patient-specific benefits and supports its role in multimodal analgesia. LEVEL OF EVIDENCE: Level II - Randomized controlled trials.