For the first time we investigate the effects that Universities exert on Total Factor Productivity dynamics for a very ample sample of 270 European regions over the period 2000-2016. This novel contribution goes beyond the traditional human capital and technological capital indirect effects and proposes a sound empirical assessment of the highly differentiated "third mission" activities. These are unique to engaged academic institutions and shape the key role they play as societal development-promoting agencies. Our analysis provides evidence of sizeable and robust universities direct supply-side effects, which complement the traditional ones in driving European regional productivity growth.