Universities have played a continued role in facilitating and enhancing the innovative potential of U.S. companies. Key to these relationships is the transfer of knowledge both from university to industry as well as from industry to university. But, few researchers have explored how different relationships necessitate specific cultural orientations, absorptive capacity abilities, and management tasks. As industry and universities engage in relationships designed to accelerate innovation it is critical to understand the factors that impact the outcomes of these relationships. Based on literature related to open innovation and industry-university relationships, an integrative explanatory theoretical framework is proposed for identifying key factors shown to play a role in the success of industry-university relationships. Applying data from a study of knowledge exchange between university and industry partners, the applicability of the framework in identifying key factors related to successful outcomes is illustrated.