Based on a comparative study of two alliances, this paper provides an in-depth examination of the role of interpartner dissimilarities in Industry-University (IU) alliances. We make a conceptual distinction between routine-based dissimilarities (differences in partners' behavior) and orientation-based dissimilarities (differences in partners' goals and expectations), illuminating their joint implications for collaborative processes and outcomes over time. Our findings reveal that interpartner dissimilarities might not be problematic at the start-up or honeymoon stage in IU alliances. In the post-formation alliance stages, however, they are likely to complicate the collaboration. Orientation-based dissimilarities might frustrate partners' attempts to solve routine-based dissimilarities by impeding successful joint sensemaking. We conclude that different combinations of the two types of dissimilarities are likely to trigger particular coordination and cooperation patterns in IU alliances, eliciting different outcomes on both technological and relational levels. (C) 2016 Elsevier B.V. All rights reserved.