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Excess reactive nitrogen (Nr), including nitrogen oxides (NO
x
) and ammonia (NH
3
), contributes strongly to fine particulate matter (PM
2.5
) air pollution in Europe, posing challenges to public health. Designing cost-effective Nr control roadmaps for PM
2.5
mitigation requires considering both mitigation efficiencies and implementation costs. Here we identify optimal Nr control pathways for Europe by integrating emission estimations, air quality modeling, exposure-mortality modeling, Nr control experiments and cost data. We find that phasing out Nr emissions would reduce PM
2.5
by 2.3 ± 1.2 μg·m
−3
in Europe, helping many locations achieve the World Health Organization (WHO) guidelines and reducing PM
2.5
-related premature deaths by almost 100 thousand in 2015. Low-ambition NH
3
controls have similar PM
2.5
mitigation efficiencies as NO
x
in Eastern Europe, but are less effective in Western Europe until reductions exceed 40%. The efficiency for NH
3
controls increases at high-ambition reductions while NO
x
slightly decreases. When costs are considered, strategies for both regions uniformly shift in favor of NH
3
controls, as NH
3
controls up to 50% remain 5-11 times more cost-effective than NO
x
per unit PM
2.5
reduction, emphasizing the priority of NH
3
control policies for Europe.
Reactive nitrogen (Nr) contributes strongly to PM
2.5
air pollution in Europe. Here, authors identify diverse Nr control pathways for Europe depending on emission and pollution formation and a priority of NH
3
control when costs are considered.