Two hundred ninety-six patients with osteoarthritis were randomized to receive either loxoprofen sodium cataplasm (LSC) once daily (n=192) or flurbiprofen cataplasm (FPC) twice daily (n=104) for 2 weeks. The primary outcome was treatment effectiveness based on Visual Analog Scale (VAS), WOMAC global score, and Lysholm score. Secondary outcomes included changes in VAS, WOMAC subdomains (pain, stiffness, physical function), and adverse events. Outcomes were assessed at 2 weeks. Overall, the results revealed significantly higher treatment effectiveness with LSC compared to FPC across all primary metrics (VAS: 74.46% vs 43.14%; WOMAC: 61.41% vs 31.37%; Lysholm: 85.25% vs 66.67%; all P<0.001). LSC also led to greater reductions in pain and better functional outcomes, with fewer dressing-related adverse events. These findings suggest that LSC is more effective than FPC for short-term symptom relief in osteoarthritis with a comparable safety profile.