BACKGROUND: Multi-Criteria Decision Analysis (MCDA) is increasingly used for decision-making in healthcare. However, its application in different decision-making contexts is still unclear. OBJECTIVES: To provide a comprehensive review of MCDA studies performed in healthcare and to summarise its application in different decision contexts. METHODS: We updated a systematic review conducted in 2013 by searching EMBASE, Medline and Google Scholar for MCDA-based evaluations in healthcare, published in English between August 2013 and November 2020. We also expanded the search by reviewing grey literature found via Trip Medical Database and Google, published between January 1990 and November 2020. A comprehensive template was developed to extract information about the decision context, criteria, methods, stakeholders involved, and the sensitivity analyses conducted. RESULTS: From the 4,295 identified studies, 473 studies were eligible for full-text review after assessing titles and abstracts. Of those, 228 studies met inclusion criteria and underwent data extraction. The use of MCDA continues to grow in healthcare literature, with most (49%) of the studies informing priority-setting decisions. Safety, cost and quality of care delivery are the most frequently used criteria, although there are considerable differences across decision contexts. Almost half of the MCDA studies used the linear-additive model while, scales and the analytic hierarchy process were the most used techniques for scoring and weighting, respectively. Considerable flaws in the application and reporting of the methods were found. CONCLUSIONS: A guide on how to conduct and report MCDA that acknowledges the particularities of the different decision contexts and methods needs to be developed.