Differences in status and powers among the constituent units of a federal (or decentralised) state are likely to create inter-regional tensions. Yet, little attention has been paid to those tensions and their impact on the territorial dynamics and constitutional evolution of the system. The proposed paper brings a new perspective into the empirical analysis of asymmetry in Canada and Spain. I set out to examine how Canadian and Spanish regions react to demands of asymmetry raised by Quebec and Catalonia, in an attempt to establish (1) the very occurrence of different types of reactions and (2) the conditions under which asymmetry is more likely to be accepted or rejected. From a methodological point of view, this work corroborates the advantages of complex causality underlying QCA. The results demonstrate that reactions to asymmetrical autonomy cannot be satisfactorily explained by individual causal factors but by certain combinations of socio-economic and political conditions.