abstract Objective: To evaluate the effectiveness and safety of synovitis granules in the treatment of knee osteoarthritis. Method: A randomized, double-blind, placebo-controlled, multicenter trial design was used. A total of 491 patients with knee osteoarthritis were included. They were divided into a synovitis granule group of 368 cases (experimental group) and a placebo group of 123 cases (control group) in a 3:1 ratio. Both groups were treated with medication for 12 weeks, 1 bag/dose, 3 times/day, and were followed up to 24 weeks. The main efficacy indicators of the study were the total score changes on the Western Ontario and McMaster Universities (WOMAC) scale after 4, 8, and 12 weeks of medication use; The secondary efficacy indicators were pain, knee joint swelling value, knee joint ultrasound fluid accumulation and synovial thickness after 4 weeks, 8 weeks, and 12 weeks of medication, biological indicators, comprehensive efficacy, and the proportion of clinical symptom recurrence or exacerbation after 24 weeks of medication. Result: Main efficacy indicators: The decrease in WOMAC scores and the rate of change before and after treatment in the experimental group were better than those in the control group at 4, 8, and 12 weeks of medication (P<0.01); Secondary efficacy indicators: After 4 weeks, 8 weeks, and 12 weeks of medication, the swelling value, pain degree reduction value, and change rate of the knee joint in the experimental group were better than those in the control group (P<0.05). At 12 weeks of medication, the reduction value and change rate of suprapatellar sac effusion (deep) in the experimental group were significantly higher than those in the control group (P<0.01), with values of 1.85 ± 4.34mm and 24.68 ± 48.57%, respectively; The reduction in synovial thickness of the suprapatellar capsule in the experimental group was 0.78 ± 1.66, which was better than that in the control group -0.02 ± 1.65 (P<0.05); The decrease and change rate of type II collagen carboxy terminal peptide and human interleukin-6 in the experimental group were better than those in the control group (P<0.01 and P<0.05). After 4 weeks, 8 weeks, and 12 weeks of medication, the total effective rates of the experimental group were 84.29%, 86.94%, and 92.24%, respectively, significantly higher than those of the control group (P<0.01). At 24 weeks of medication, the recurrence rate of 7.14% in the experimental group was significantly lower than that in the control group (P<0.01). Conclusion: Synovitis granules can alleviate joint swelling and pain in patients with knee osteoarthritis, improve motor dysfunction, and promote the absorption of joint effusion, improve synovial thickening, reduce the recurrence/exacerbation rate after discontinuation of medication, with fewer adverse reactions and good safety. Keywords: synovitis granules; Knee joint; Osteoarthritis KOA