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Following the increased cooperation across both territorial and administrative borders in the last decades, research on successful Inter-Organizational Relations (IORs) – such as networks, joint ventures, alliances, and partnerships – has grown considerably. Still, our knowledge about the factors and events leading to their breakdown is scarce. This chapter discusses the conceptualization of breakdown of cooperation, and how to measure it empirically. Next, a model defining explanatory factors of breakdown is sketched out. Factors are systemized in two larger groups: structural and process-based. Finally, we conduct a comparative empirical evaluation of four inter-municipal cooperative arrangements in Norway (called ‘regional councils), two experiencing breakdown, two others still in full function. The empirical study indicates that no single factor can explain breakdown of cooperation. Rather, it is a complex combination of factors being present – or not present – at the same time that seems to produce breakdown of cooperation.