19 randomized controlled trials (4485 patients) analyzing the effects of hyaluronic acid injection on pain, function and stiffness in knee osteoarthritis patients were included. The purpose of this meta-analysis was to determine the clinical significance of hyaluronic acid and which trial factors influence the treatment effects on pain, function, and stiffness. The results displayed that double-blinded, sham-controlled trials displayed smaller treatment effects than trials that were not sufficiently blinded and cross-linked hyaluronic acid displayed better treatment effects than non-cross-linked preparations. The overall treatment effect of hyaluronic acid was determined to be non-clinically important in pain function and stiffness in these 19 studies.