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Objective: Medical education should enhance empathy. We examined, using self-assessment instruments and standardized patients (SPs), the impact on empathy, of a multi-year intervention (years 4-6 of medical training) that uses reflective learning approaches., Methods: 241 final-year medical students participated; 110 from the 2018 graduation class (non-intervention group) and 131 from the 2019 graduation class (intervention group). Participants completed two self-reported empathy questionnaires - the Jefferson Scale of Empathy-Students (JSE-S) and the Interpersonal Reactivity Index (IRI) - and a personality questionnaire, the NEO Five-Factor Inventory. Additionally, SPs in a simulated station assessed participants' empathy with two patient-reported instruments: the Consultation and Relational Empathy (CARE) scale and the Jefferson Scale of Patient Perceptions of Physician Empathy (JSPPPE)., Results: Empathy scores were significantly higher in the intervention group compared to the non-intervention group when assessed by the SP (p < 0.001). No differences were found in self-reported questionnaires between the two groups., Conclusion: A longitudinal, multi-year reflection-based intervention enhanced empathy amongst medical students as assessed by SPs, but not when assessed by student self-reported measures., Practice Implications: Multi-year reflective learning interventions during clinical training nurture empathy in medical students. Assessments completed by SPs or patients may enhance the evaluation of empathy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)