 Background Traditional simulators such as cadavers, animals, or actors are becoming less common for upskilling health workers due to ethical issues, commitment to patient safety, and cost and resource restrictions. Virtual reality, VR, and augmented reality, AR, may help overcome these barriers, but their effectiveness is often contested and poorly understood. Objective The aim of this review is to develop, test, and refine an evidence-informed program theory on how, for whom, and to what extent training using AR or VR works for upskilling health care workers, and to understand what facilitates or constrains their implementation and maintenance. Methods A realist synthesis was conducted using a three-step process, theory elicitation, theory testing, and theory refinement. Literature on AR or VR used to train health care staff was searched in seven databases, and eleven practitioner journals. An initial program theory comprising of context mechanism outcome, CMO, configurations was formed through a narrative synthesis. Empirical studies were identified through a second search, and the mixed methods appraisal tool was used to assess their quality and determine confidence in each CMO configuration. Results Of the 41 CMO configurations identified, nine had moderate to high confidence based on 46 empirical studies reporting on VR, AR, or mixed simulation training programs. Realistic, high fidelity, simulations trigger perceptions of realism, easier visual. This article was authored by Narayana Gasteigar, Sabine N. Vanderveer, Paul Wilson, and others. We are article.tv, links in the description below.