Background The use of electronic medical records (EMRs)/electronic health records (EHRs) provides potential to reduce unwarranted clinical variation and thereby improve patient health care outcomes. Minimization of unwarranted clinical variation may raise and refine the standard of patient care provided and satisfy the quadruple aim of health care. Objective A systematic review of the impact of EMRs and specific subcomponents (PowerPlans/SmartSets) on variation in clinical care processes in hospital settings was undertaken to summarize the existing literature on the effects of EMRs on clinical variation and patient outcomes. Methods Articles from January 2000 to November 2020 were identified through a comprehensive search that examined EMRs/EHRs and clinical variation or PowerPlans/SmartSets. Thirty-six articles met the inclusion criteria. Articles were examined for evidence for EMR-induced changes in variation and effects on health care outcomes and mapped to the quadruple aim of health care. Results Most of the studies reported positive effects of EMR-related interventions (30/36, 83%). All of the 36 included studies discussed clinical variation, but only half measured it (18/36, 50%). Those studies that measured variation generally examined how changes to variation affected individual patient care (11/36, 31%) or costs (9/36, 25%), while other outcomes (population health and clinician experience) were seldom studied. High-quality study designs were rare. Conclusions The literature provides some evidence that EMRs can help reduce unwarranted clinical variation and thereby improve health care outcomes. However, the evidence is surprisingly thin because of insufficient attention to the measurement of clinical variation, and to the chain of evidence from EMRs to variation in clinical practices to health care outcomes.