AbstractExcess reactive nitrogen (Nr), including nitrogen oxides (NO_x) and ammonia (NH₃), 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 NH₃ 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 NH₃ controls increases at high-ambition reductions while NO_x slightly decreases. When costs are considered, strategies for both regions uniformly shift in favor of NH₃ controls, as NH₃ controls up to 50% remain 5-11 times more cost-effective than NO_x per unit PM_2.5 reduction, emphasizing the priority of NH₃ control policies for Europe.