Objective.To evaluate the efficacy and safety of glucosamine(GS)combined with chondroitin sulfate(CS)for knee OA.Methods.We included RCT of GS combined with CS for knee OA.The primary outcome were WOMAC(0-100).We searched the CENTRAL,PUBMED,EMBASE and CBM(search date Janurary,2016).The Review manager 5.3 software was used for data analysis.Results.The search retrieved 867 titles,of which 4 RCTs were included in this systematic review.The overall risk of bias was low in 3 trials.Four RCTs(n=1145)compared combination with GS and 3(n=1067)compared combination with CS.The outcomes analysis showed:(1)Summarized results of 3 RCTs(n=1009)showed no significant difference between combination and GS.MDs of WOMAC score in pain,stiffness and function were-6.60(95%CI-18.79,5.59),-15.90(-43.09,11.29)and-6.44(-16.46,3.59),respectively.(2)Two study(n=937)compared combination with CS and showed no significant difference.Pooled MD of WOMAC score in pain and function were-0.80(-4.96,3.36)and-1.76(-4.46,0.94)respectively.(3)Subgroup analysis in 1 RCT showed that in moderate-to-severe knee pain group(n=142)combination obviously improve the WOMAC score compared with either GS or CS.Conclusions.There is no evidence to support GS combined with CS for knee OA can improve the WOMAC score compared with either GS or CS.For patients with moderate-to-severe knee pain,combination might be superior to either GS or CS.