The management of international rivers is increasingly marked by a heightened attention to and growth in institutions at the river-basin level to promote cooperation and resolve conflicts between states in a basin. Yet, little theoretical and empirical research exists to understand when these institutions are most effective. Here we draw from diverse literatures, including work on social and ecological systems, international institutions, common-pool resources, and international waters, to capture and integrate the design elements associated with effective collaborative management along an international river. We apply and test the validity of our model in a plausibility probe through the analysis of the conflict between Argentina and Uruguay over the construction of pulp mills along the Uruguay River, and the role of the established and functioning river basin organization—the Administrative Commission of the Uruguay River (CARU)—in this conflict. We re-examine our model based on our case findings to highlight the challenge and role of public input and representation in institutional effectiveness along international rivers.