The study presents a change of innovation model in the highly developed region of the European Union Friuli Venezia Giulia in Italy. The paper presents the innovation system and the outline of the region’s economic history, as well as the factors that preceded the change in innovation model, the direct causes of the change, and the impact of institutional factors as well as the development barriers. The analyzes were based on interviews with 14 representatives of regional and local authorities, innovation and entrepreneurship support institutions, universities, R&D units and a cluster from the region, as well as statistical data and source material.