The purpose of this study is to identify the determinants of innovation of enterprises in the Regional Innovation System context. We analyse factors that determine regional innovation in a less developed region, taking the Podkarpackie region in Poland as our empirical counterpart. We examine how the EU economic policy instruments influence the innovation of enterprises within the context of the Regional Innovation Systems. We propose a model for the implementation of innovations and test our hypotheses based on the data drawn from the period of 2011–2014. The paper provides insights on a rather successful story from Poland. We posit that enterprises use only specific public policy instruments and that companies’ demand for innovation-supporting instruments changes, reacting to the business cycle phase and to financial incentives.