Democracies have experienced two trends in the last decades: the growing personalization of politics and the increasing relevance of regions in the political process. This article addresses these trends by posing two questions: Do political leaders influence the vote in regional elections? Do regional party leaders have a larger impact on voter preferences than their national counterparts in regional elections? To answer these questions, we analyzed five regional elections held in Andalusia between 2004 and 2018. The results show that both national and regional leaders matter in regional elections. However, the effect of national and regional leaders is “conditioned” by the characteristics of the leaders themselves, their respective parties, and citizens’ party attachments. Additionally, there is no clear evidence that the type of relationship between national and regional leaders of the same party—cohesion-like or confrontation-like—and the electoral context variables may affect the voting decision in multi-level government systems.