ObjectivesTo provide an overview of whether the clinical decision support system (CDSS) was effective in reducing medication error and improving medication safety and to assess the quality of available scientific evidence.MethodsPubMed, EMbase, The Cochrane Library, CBM, WanFang Data, VIP and CNKI databases were electronically searched to collect systematic reviews (SRs) on application of clinical decision support system in the medication error and safety from January, 1996 to November, 2018. Two reviewers independently screened literature, extracted data and then evaluated methodological quality of included SRs by using AMSTAR tool.g AMSTAR tool.ResultsA total of 20 SRs including 256 980 healthcare practitioners and 1 683 675 patients were included. Specifically, 16 studies demonstrated moderate quality and 4 demonstrated high quality. 19 SRs evaluated multiple process of care outcome: 9 were sufficient evidence, 6 were limited evidence, and 7 were insufficient evidence which proved that CDSS had a positive effect on process outcome. 13 SRs evaluated reported patient outcomes: 1 with sufficient evidence, 3 with limited evidence, and 9 without sufficient evidence.ConclusionsCDSS reduces medication error by inconsistently improving process of care measures and seldom improving patient outcomes. Larger samples and longer-term studies are required to ensure a larger and more reliable evidence base on the effects of CDSS intervention on patient outcomes.