What mechanisms explain the voting defection of Members of the European Parliament (MEPs) from their European party groups? Previous literature shows that when the ideological position of an MEP’s national party differs from that of the European party group, the national party is the primary principal that influences MEPs’ voting behaviour in the European Parliament. However, the empirical evidence is somewhat sporadic, and there has been a considerably high voting cohesion among MEPs within EP groups over time. Against this backdrop, I investigate under what conditions the greater ideological distance between national parties and EP groups leads to MEPs’ voting defection from their EP groups. Taking an issue-specific approach, I argue that the effect of ideological distance depends on the level of issue salience to national parties and proximity to European elections. Conducting a multi-level logistic regression analysis on the individual MEPs’ voting decisions in the 7th–9th European Parliament (from 2009 to 2022) across six different policy areas, I find that greater policy distance between the national party and the EP group increases the probability of an individual MEP voting against the majority of the EP group, particularly on issues that the national party prioritizes in its election manifesto. Furthermore, MEPs are more likely to defect from their EP groups when the next European Parliament elections are proximate and the ideological divergence between their two principals is more pronounced. This research has important implications for our understanding of legislative behaviour, party competition, and the politicization of Europe.