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Background  Systematic reviews involve searching multiple bibliographic databases to identify eligible studies. As this type of evidence synthesis is increasingly pursued, the use of various electronic platforms can help researchers improve the efficiency and quality of their research. We examined the accuracy and efficiency of commonly used electronic methods for flagging and removing duplicate references during this process.    Methods  A heterogeneous sample of references was obtained by conducting a similar topical search in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and PsycINFO databases. References were de-duplicated via manual abstraction to create a benchmark set. The default settings were then used in Ovid multifile search, EndNote desktop, Mendeley, Zotero, Covidence, and Rayyan to de-duplicate the sample of references independently. Using the benchmark set as reference, the number of false-negative and false-positive duplicate references for each method was identified, and accuracy, sensitivity, and specificity were determined.    Results  We found that the most accurate methods for identifying duplicate references were Ovid, Covidence, and Rayyan. Ovid and Covidence possessed the highest specificity for identifying duplicate references, while Rayyan demonstrated the highest sensitivity.    Conclusion  This study reveals the strengths and weaknesses of commonly used de-duplication methods and provides strategies for improving their performance to avoid unintentionally removing eligible studies and introducing bias into systematic reviews. Along with availability, ease-of-use, functionality, and capability, these findings are important to consider when researchers are selecting database platforms and supporting software programs for conducting systematic reviews.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13643-021-01583-y.

Considerations for conducting systematic reviews: evaluating the performance of different methods for de-duplicating references