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Although nurses comprise the largest group of health professionals and electronic health record (EHR) user base, it is unclear how EHR use has affected nurse well-being. This systematic review assesses the multivariable (ie, organizational, nurse, and health information technology [IT]) factors associated with EHR-related nurse well-being and identifies potential improvements recommended by frontline nurses. We searched MEDLINE, Embase, CINAHL, PsycINFO, ProQuest, and Web of Science for literature reporting on EHR use, nurses, and well-