University-industry R&D collaboration is a key driver of participating firms’ technological capability. However, there is still debate on the determinants of a firm’s innovation performance, especially in relation to the characteristics of collaboration and organizational slack. We lay the foundation for our theoretical framework by establishing testable hypotheses on how the characteristics of university-industry collaboration and organizational slack affect participating firms’ innovation performance. Based on a panel data of 2914 firm-year cases for the top 200 U.S. R&D firms, estimates obtained from quantitative techniques produce consistent results and support our predictions. Collaboration breadth, network centrality, unabsorbed slack, collaboration experience and collaboration proactiveness are associated with innovation performance. Moreover, a firm’s higher absorbed slack exerts a negative influence on innovation performance. The managerial implications and future research directions are discussed.