Objective To evaluate the clinical effects of intra-articular injection of autologous adipose derived stem cells (ADSCs) or ADSCs combined with hyaluronate acid (HA) for knee osteoarthritis.Methods From May 2013 to May 2015,a total of 108 patients with knee osteoarthritis (Kellgren-Lawrence grades:1-3) were recruited in the present study.The patients were randomly divided into three groups:ADSCs,HA and ADSCs+HA.All patients (36 cases in each group) were injected with the drug in the joint cavity once a week for three weeks.The methods used for evaluating the clinical manifestations and joint damage on MRI included visual analogue scale (VAS),Western Ontario and McMaster University (WOMAC) osteoarthritis index and whole-organ magnetic resonance imaging score (WORMS).Evaluations were conducted before injection and at 3,6,12,24 and 36 months after injection.Results All patients were followed up for 36 months without any dissociation.No adverse reaction was observed during the treatment and at the follow-up duration.The VAS score and WOMAC total score of the ADSCs group and the ADSCs+HA group were better than those in the HA group at each time point after injection (P＜0.05).The average VAS of the ADSCs group decreased from 4.14±1.42 at pre-injection to 2.39±1.74 at 36 months after injection.The WOMAC total score decreased from 42.86± 31.24 to 27.17±27.99.The average VAS in the ADSCs+HA group decreased from 4.25±1.13 to 2.31±1.74,and the WOMAC total score decreased from 34.92±22.62 to 21.33±21.38.However,the average VAS and WOMAC total score of the HA group at 36 months after injection were higher than those before the injection.In terms of the VAS at 3 months after injection,the ADSCs+HA group scored better than that of the ADSCs group (P＜0.05).There was no significant difference in WOMAC scores between the ADSCs and ADSCs+HA groups at each time point after injection (P＞0.05).The WORMS cartilage injury score improved in 10 patients with ADSCs after injection (P＜0.05).The subchondral bone wear score improved as well (P＜0.05).The difference of WORMS cartilage injury scores before and after injection was correlated with the difference of the WOMAC total score (r=0.790,P=0.007) and that of VAS score difference (r=0.800,P=0.005).Conclusion Autologous ADSCs and ADSCs combined with HA intra-articular injections can effectively relieve pain and improve function of patients with knee osteoarthritis for 36 months.In addition,ADSCs combined with HA injections can relieve pain more effectively within a short duration.Cartilage repair is associated with joint function improvement.