This study empirically examines the determinants of heterogeneous firm-level cooperative R&D commercialization strategies. While the volume of interfirm collaboration has increased dramatically in recent decades, the determinants of firm-level choices among alternate modes of such cooperative activity remain relatively understudied. We develop a conceptual model of factors determining collaborative mode choice at the organizational portfolio level. These factors include the firm-level appropriation environment, in which deal-level choices have portfolio-level spillover implications, as well as governance capabilities developed by the firm over time. Using a random sample of innovating biotechnology start-ups, we assemble a firm-year panel dataset that aggregates transaction-level collaboration data to the firm-year level, allowing us to characterize firms' portfolios of collaborative deals. We find broad empirical support for our model, suggesting that a firm's appropriation environment and governance capabilities strongly influence portfolio-level collaboration mode choices. In addition, we explore the implications of governance capability development, finding that experience with particular modes, as well as deviations from existing capabilities, impact firm valuation. Copyright © 2009 John Wiley & Sons, Ltd.