Background: Regional medical campuses (RMCs) create positive economic impacts in communities and small cities. RMCs increase educational capacity, medical services, and address the shortage or maldistribution of physicians in rural areas. Our paper answers the question: How do you assess the economic impact of a RMC? Methods: The Canadian Input-Output (I-O) model and the Simplified American Council on Education (ACE) model are adapted to assess the economic impact of an individual RMC using a step-by-step process. The models are tested using data from three Canadian RMCs. Results: A comparison of the two models found similarities with data requirements and spreadsheet calculations. However, the Canadian I-O model spreadsheet is linked to Statistics Canada multipliers and calculations are more complex. Outputs are calculated for multiple economic variables. The Simplified ACE model, in contrast, uses a single multiplier and provides a single number by input category and a cumulative total of all impacts. Conclusion: Both models successfully assess economic impacts of RMC. The step-by-step process allows RMC administrators and others to understand the limitations of each model, but also facilitates an in-house economic assessment of RMC. The authors provide guidance on choosing the best model.