Abstract Introduction Air pollution (AP) is becoming an increasingly important non-classical CVD risk factor. Recent years have brought us the introduction of new types of AP, such as ‘Polish smog’, rich in particulate matter (PM) and benzo(alpha)pyrene (B(a)P) - thus far overlooked in scientific research. Acute ischemic stroke (AIS) is an increasing healthcare challenge, with the ageing population and associated presence of atrial fibrillation worldwide. Intravenous thrombolysis (IVT), alongside thrombectomy, is the most effective AIS treatment method. Purpose To analyze the impact of AP on AIS requiring IVT incidence. To our knowledge this is the first study of its kind worldwide. Methods The study covered 500 municipalities inhabited by 5.7 million people in Poland in 2011-2020. AIS requiring IVT incidence data [hospitalizations with ICD-10 diagnosis (I63.X) and concomitant ICD-9 procedure (99.101/99.102/99.103)] and AP concentrations (PM2.5 and B(a)P) were obtained from the National Health Fund and Inspectorate for Environmental Protection, respectively. IVT was administered within 4.5 hours from the onset of AIS symptoms, ensuring accuracy in the timing of exposure. Using the GEM-AQ model we calculated AP levels for all 500 municipalities. To analyze the effects of AP we used quasi-Poisson generalized additive models with covariates such as weather conditions, day of the week, bank holidays, and seasonal trends. Results are presented as relative risks (RRs) and 95% confidence intervals (95% CI) per interquartile range increase in AP on the day of exposure (LAG 0) and the following days (LAG 1, etc). Results In the study period, we recorded 96,122 AIS with a slight predominance of females (52.6%) and median age 76 years old (y.o) [IQR 66-83]; 10,486 (10.9%) were treated with IVT (median age 74 y.o. IQR 65-82), females 51.3%. Mortality rates were lower in patients treated with IVT than overall AIS patients (13.3% vs 15.4%, p<0.001). Exposure to B(a)P was associated with the highest increase in AIS requiring IVT incidence on LAG 0 and this effect persisted for up to 3 days after exposure [Figure 1]. In the overall population, an increase in PM2.5 concentration was associated with an increased risk of AIS requiring IVT on LAG 0, LAG 1, and LAG 3 [Figure 1]. AP increased the risk of AIS requiring IVT in both young and older individuals, as well as in women and men. We recorded no differences between the effects of analyzed air pollutants and AIS requiring IVT depending on age and sex [Figure 2]. Conclusions AP acts as a trigger for AIS requiring IVT with a similar impact regardless of sex and age. Patients undergoing IVT are characterized by better survival. Public health changes should consider efforts to decrease levels of air pollutants. Highly polluted areas should have centers with rapid access to AIS treatments and our study could help to identify high risk areas that require adaptations in local infrastructure.Figure 1.Figure 2.