In the past few years, the world has witnessed an unprecedented popular backlash against international institutions. Popular demands to not only slow down, but to reverse international integration have proliferated, and have resulted in referendum and election outcomes that have reverberated across the world. Examples range from the Swiss 2014 mass immigration initiative over the British 2016 Brexit referendum to the 2016 election of a US President seemingly determined to withdraw US support from various international treaties. The implications of these mass-based disintegration efforts reach far beyond the countries in which they originate. First, the disintegration process is shaped by how remaining member states respond to one member’s bid to unilaterally change or terminate the terms of an existing international agreement. Second, mass-based disintegration bids also pose considerable risks of political contagion by encouraging disintegrative tendencies in other countries. Yet despite their disruptive nature, very little research exists beyond individual case studies on the general drivers, dynamics and challenges these instances of mass-based disintegration pose for international cooperation. This paper therefore engages in a comparative inquiry into the mass politics of disintegration that pays particular attention to the strategic dilemmas these instances pose for the affected international institutions and their remaining member states. It argues that the remaining member states have incentives to intervene in domestic campaigns in which disintegration figures as a viable outcome, but that the difficulties of successful intervention are considerable. It also shows that after a vote in favor of disintegration, the remaining member states face an “accommodation dilemma” between preserving as many cooperation gains as possible and making exit costly in order to discourage other member states from following suit.