BackgroundComputerised decision support systems (CDSS) are widely used by nurses and allied health professionals but their effect on clinical performance and patient outcomes is uncertain.ObjectivesEvaluate the effects of clinical decision support systems use on nurses’, midwives’ and allied health professionals’ performance and patient outcomes and sense-check the results with developers and users.Eligibility criteriaComparative studies (randomised controlled trials (RCTs), non-randomised trials, controlled before-and-after (CBA) studies, interrupted time series (ITS) and repeated measures studies comparing) of CDSS versus usual care from nurses, midwives or other allied health professionals.Information sourcesNineteen bibliographic databases searched October 2019 and February 2021.Risk of biasAssessed using structured risk of bias guidelines; almost all included studies were at high risk of bias.Synthesis of resultsHeterogeneity between interventions and outcomes necessitated narrative synthesis and grouping by: similarity in focus or CDSS-type, targeted health professionals, patient group, outcomes reported and study design.Included studiesOf 36,106 initial records, 262 studies were assessed for eligibility, with 35 included: 28 RCTs (80%), 3 CBA studies (8.6%), 3 ITS (8.6%) and 1 non-randomised trial, a total of 1318 health professionals and 67,595 patient participants. Few studies were multi-site and most focused on decision-making by nurses (71%) or paramedics (5.7%). Standalone, computer-based CDSS featured in 88.7% of the studies; only 8.6% of the studies involved ‘smart’ mobile or handheld technology. Care processes – including adherence to guidance – were positively influenced in 47% of the measures adopted. For example, nurses’ adherence to hand disinfection guidance, insulin dosing, on-time blood sampling, and documenting care were improved if they used CDSS. Patient care outcomes were statistically – if not always clinically – significantly improved in 40.7% of indicators. For example, lower numbers of falls and pressure ulcers, better glycaemic control, screening of malnutrition and obesity, and accurate triaging were features of professionals using CDSS compared to those who were not.Evidence limitationsAllied health professionals (AHPs) were underrepresented compared to nurses; systems, studies and outcomes were heterogeneous, preventing statistical aggregation; very wide confidence intervals around effects meant clinical significance was questionable; decision and implementation theory that would have helped interpret effects – including null effects – was largely absent; economic data were scant and diverse, preventing estimation of overall cost-effectiveness.InterpretationCDSS can positively influence selected aspects of nurses’, midwives’ and AHPs’ performance and care outcomes. Comparative research is generally of low quality and outcomes wide ranging and heterogeneous. After more than a decade of synthesised research into CDSS in healthcare professions other than medicine, the effect on processes and outcomes remains uncertain. Higher-quality, theoretically informed, evaluative research that addresses the economics of CDSS development and implementation is still required.Future workDeveloping nursing CDSS and primary research evaluation.FundingThis project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in Health and Social Care Delivery Research; 2023. See the NIHR Journals Library website for further project information.RegistrationPROSPERO [number: CRD42019147773].