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Background: Computerized clinical decision support systems are used by clinicians at the point of care to improve quality of healthcare processes (prescribing error prevention, adherence to clinical guidelines, etc.) and clinical outcomes (preventive, therapeutic, and diagnostics). Attempts to summarize results of computerized clinical decision support systems to support prescription in primary care have been challenging, and most systematic reviews and meta-analyses failed due to an extremely high degree of heterogeneity present among the included primary studies. The aim of our study will be to synthesize the evidence, considering all methodological factors that could explain these differences, and build an evidence and gap map to identify important remaining research questions., Methods: A literature search will be conducted from January 2010 onwards in MEDLINE, Embase, the Cochrane Library, and Web of Science databases. Two reviewers will independently screen all citations, full text, and abstract data. The study methodological quality and risk of bias will be appraised using appropriate tools if applicable. A flow diagram with the screened studies will be presented, and all included studies will be displayed using interactive evidence and gap maps. Results will be reported in accordance with recommendations from the Campbell Collaboration on the development of evidence and gap maps., Discussion: Evidence behind computerized clinical decision support systems to support prescription use in primary care has so far been difficult to be synthesized. Evidence and gap maps represent an innovative approach that has emerged and is increasingly being used to address a broader research question, where multiple types of intervention and outcomes reported may be evaluated. Broad inclusion criteria have been chosen with regard to study designs, in order to collect all available information. Regarding the limitations, we will only include English and Spanish language studies from the last 10 years, we will not perform a grey literature search, and we will not carry out a meta-analysis due to the predictable heterogeneity of available studies., Systematic Review Registration: This study is registered in Open Science Framework https://bit.ly/2RqKrWp., (© 2022. The Author(s).)