This randomized, controlled study compared the efficacy and safety between oxycodone-paracetamol tablet and celecoxib for postoperative analgesia in patients who underwent arthroscopic knee surgery (AKS). Totally, 232 patients scheduled to undergo AKS were enrolled and were randomly assigned to either the oxycodone-paracetamol (OPT group) or the celecoxib group (CEL group). Pain at rest/motion (based on pain visual analog scale (VAS) score), rescue analgesia consumption, satisfaction level and adverse events were assessed after AKS. Pain VAS score at rest was decreased at 6 h, 12 h post-AKS in the OPT group compared with the CEL group. Similarly, pain VAS score at motion was reduced at 6 h, 12 h, 24 h post-AKS in the OPT group compared to the CEL group. Furthermore, both rescue analgesia rate (14.7% vs. 33.6%) and accumulated pethidine consumption (3.7 ± 8.9 mg vs. 14.0 ± 21.2 mg) were lower in OPT group compared with the CEL group. Patients satisfaction score was either at 24 h, 48 h in OPT group compared with the CEL group. Further subgroup analyses indicated that the effect of oxycodone-paracetamol versus (vs. celecoxib) on post-AKS management was more apparent in the elderly patients and male patients. In addition, the adverse events were well tolerable (including nausea, constipation, vomiting, drowsiness and dizziness) and were of no different between the two groups. In conclusion, oxycodone-paracetamol tablet presents increased analgesic efficacy for acute postoperative pain, with higher patient satisfaction and comparable safety profiles compared with celecoxib in patients underwent AKS.