Introduction: decision-making about when MEs replacement should take place is a traditional hospital challenge due to its high cost for health institutions and the risk it could represent in any existing medical care practice or procedure. The Health Technology Assessment (HTA) for MEs allows prioritizing its replacement in a hospital. Most MEs replacement evaluations focus solely on cost analyses; however, these evaluations do not consider the full role that MEs play in the healthcare processes In this sense, the investment cost of the equipment and other critical factors to evaluate the process, costs and productivity must be considered either. Objective: this paper proposes a methodology to support the decision to replace or not MEs, based on economic evaluation and business process analysis. Material and methods: cost-effectiveness, intermediate effectiveness, and process workflow analysis are applied. The best MEs alternative is identified through a decision-tree and time indexes, productivity and performance indicators. This methodology was tested by evaluating, as a case study, whether it is necessary to replace the sterilizers/washing machine that are in the last stage of their lifecycle, operating in our Central Sterilization Units. Results: the methodology presented in this paper has a high potential to detect delays, measure efficiency, productivity and costs of the processes, and even, based on the workflow analysis, to be able to improve the processes where MEs are operating. Conclusion: furthermore, HTA-based MEs replacement methodology allows to generate cost-effective information for decision-making at the management level.How to cite: Navor-Galeana NP, Pineda C, Sandoval H, Gutiérrez-Martínez J. Methodology for the replacement of high-tech medical equipment, applying economic evaluation and business process analysis.