BACKGROUND The interspace between the popliteal artery and posterior capsule of the knee block (IPACK) combined with adductor canal block (ACB) has short-term analgesic effect after arthroscopic knee surgery(AKS), and prolonging the duration of analgesia is very important for patients to recover quickly after surgery. The purpose of this study was to investigate whether perineural dexmedetomidine (DEX) or intravenous can prolong the analgesic time of IPACK and ACB, and ultimately promote the postoperative rehabilitation of patients undergoing AKS. MATERIAL AND METHODS In this randomized controlled trial, 102 eligible AKS patients were allocated to 3 groups: perineural DEX with ropivacaine for Group E (n=34), intravenous DEX for Group I (n=34), and standard IPACK-ACB (ropivacaine alone) for Group C (n=34). The outcomes included resting and active Visual Analog Scale (VAS) scores at 6 h, 12 h, 24 h, 48 h, 54 h, and 60 h postoperatively, inflammatory marker levels on the first postoperative day, and maximum walking distance at 24 and 48 hours after surgery. RESULTS There were no significant demographic differences between the 3 groups. Resting and active VAS scores in Group E were significantly lower than those in Group C within 48 hours postoperatively (P<0.05), VAS at 48 h resting state (P<0.001, mean difference,-1.15; 95% CI, -1.65 to -0.65), VAS at 48 h active state (P<0.001, mean difference,-0.91; 95% CI, -1.32 to -0.50). On the first postoperative day, IL-1β levels in Groups E and I were significantly lower than in Group C (P<0.05). Group E had a significantly longer maximum walking distance at 24 and 48 hours after surgery compared to Groups I and C (P<0.001). CONCLUSIONS Perineural DEX prolongs IPACK-ACB analgesia to 48 hours, improves functional recovery, and attenuates IL-1β release, outperforming intravenous administration. These findings support the integration of route-specific DEX into enhanced recovery protocols for AKS.