PURPOSE: Interspace infiltration between the posterior knee capsule and popliteal artery (iPACK) is an effective method for pain control following total knee arthroplasty (TKA). However, this procedure still requires an experienced physician to perform ultrasound-guided injections postoperatively, and the patient will need to undergo additional injections aside from the surgery. This study investigates a novel, simplified intraoperative iPACK (I-iPACK) technique, applied during surgery without the need for ultrasound or an anesthesiologist. We hypothesized that combining I-iPACK with periarticular injection (PAI), comparing with using PAI alone, could reduce postoperative morphine consumption and improve the range of motion (ROM) in patients after TKA. METHODS: This retrospective analysis reviewed data from 600 patients who underwent unilateral TKA, selected from an initial pool of 3502. The patients were divided into two groups: 300 received PAI with I-iPACK (Group A), and 300 received PAI alone (Group B). The groups were matched by age and gender. The primary outcome parameters postoperative pain levels (VAS scores) and cumulative morphine consumption at 24, 48, and 72 h. The secondary outcome parameters were maximum tolerated ROM measured by continuous passive motion (CPM) through time and adverse events, such as nausea, dizziness, constipation, and gastrointestinal bleeding, monitored for two weeks post-surgery. The hypothesis is the additional I-iPACK technique is not inferior to the PAI alone. Non-parametric statistical methods were used for analysis, with a significance threshold set at p <
0.05. RESULTS: Both groups were comparable in demographics, and no significant differences in surgery time were noted. However, the I-iPACK group had significantly less blood loss. Patients receiving I-iPACK had improved ROM at 24 h, reduced morphine consumption at all measured time points, and had lower rates of complications including constipation and dizziness. The two groups showed no significant differences in other complications or pain scores. CONCLUSION: The addition of I-iPACK to PAI during TKA surgery effectively reduces morphine consumption, limits blood loss, and enhances early postoperative ROM without increasing adverse events such as nerve palsy. Similar technique of intra-operative infiltration for pain control could be adopted in diverse surgical settings. However, the lack of blinding might have minor impacts on the patient-reported outcome such as VAS scores. LEVEL OF EVIDENCE: Level III, Therapeutic Study.