Corporate governance issues are critical in university spin-offs because, since their substantially knowledge and technology-driven nature, investments are characterized by rapid growth and real investment opportunities, affecting innovative activity too. In this view, the paper investigate the role of the board of directors’ composition on innovation performance of university spin-offs. Based on a panel sample of 478 Italian university spin-offs, the results show that board size has an inverted-U-shaped relationship with innovation, remarking that not too large boards are more efficient and work better, influencing in a positive way the innovation activity of the spin-off. Regarding the impact of the outside directors, the results seems to invalidate its positive and significant effect on innovation performance. Also the CEO-duality seems to have no influence on the innovative activity. These findings may represent potential indicators of the optimal configuration for board in university spin-offs in order to improve innovation.