Higher education institutions and, particularly, polytechnic institutes in Portugal are, generally speaking, recognized as the key stakeholders in regional development. However, due to the economic recession of recent years and the consequent budget constraints, higher education institutions more than ever need to demonstrate the social and cultural impact of their activities within their communities and their contribution to its economic development. The aim of this paper is to estimate the economic impact of a group of polytechnic institutes located in regions with diverse socio-economic characteristics using a common methodology. This common framework enables a comparative study and a better identification of the variables that differentiate the different regions, the respective polytechnics and their impacts.