Background:Ambient air pollution has been widely linked with morbidity and mortality of stroke. However, its effects on dynamic progression trajectory of stroke remain unknown.Objective:To investigate the effects of ambient air pollution on progression trajectory from healthy to incident stroke, post-stroke cardiovascular diseases, and subsequent death.Methods:We retrieved 318,752 participants from the UK Biobank. The annual concentrations of air pollution [particulate matter (PM2.5, PMcoarse, PM10 and PM2.5 absorbance), nitrogen dioxide (NO2), and nitrogen oxides (NOx)] were estimated through land-use regressions. A multi-state regression model was employed to investigate the effects of air pollution on each stage of the progression of stroke.Results:During 3,765,630 person-years of follow-up, we identified 5,967 incident stroke patients, 2,985 post-stroke cardiovascular patients, and 1,020 deaths afterward. Each 5 μg/m3 increase in PM2.5, NO2, and NOx was associated with the transition from healthy to incident stroke [Hazard Ratios (HRs) (95% confidence intervals (CI)) = 1.24 (1.10, 1.40); 1.02 (1.00, 1.03); 1.01 (1.00, 1.02)] and transitions from healthy to death directly [1.30 (1.21, 1.40); 1.03 (1.02, 1.04); 1.02 (1.01, 1.02)]. We also observed positive associations for post-stroke CVDs, especially for NO2 [1.04 (95% CI: 1.02, 1.06)], but these effects gradually declined for mortality outcome.Conclusion:This study provides the first evidence that ambient air pollution is one important factor associated with the progression of stroke, and the effects differed across different clinical stages. A better understanding of the differential effects of air pollutants on different stroke transition stages could provide valuable insight toward targets for health management and clinical prevention.