Abstract Background Ischemic stroke after coronary angiography is a life-threatening complication, leading to high mortality and long-term sequelae in surviving patients. Contemporary data from a European nationwide perspective are however lacking. Purpose We aimed to investigate the incidence, temporal trends, and outcome of ischemic stroke complicating coronary angiography in a German nationwide cohort. Methods A retrospective analysis of healthcare records from 2006–2020 based on ICD-10 and OPS codes obtained from the German Federal Statistical Office was carried out. Patients ≥18 years of age hospitalized for coronary angiography (both diagnostic and percutaneous interventions) were included in this analysis. Ischemic stroke events as well as co-morbidities were identified using ICD-10 and OPS codes. The outcome of interest was in-hospital mortality. Multivariable logistic regressions were computed for the association of ischemic stroke with in-hospital mortality adjusting for age, gender, hypertension, hyperlipoproteinemia, and diabetes mellitus. Results Overall 5,098,751 cases of patients undergoing coronary angiography (mean age 68.7±11.4 years; 28.0% female) between 2006 and 2020 were included. Ischemic stroke occurred in 3,808 (0.07%) patients. In comparison, individuals who suffered from peri-interventional ischemic stroke were older (70.8±11.1 vs. 68.7±11.4; p<0.001), more likely female (33.4% vs. 27.9%; p<0.001), and differed significantly according to their clinical characteristics (see Table 1). Patients with ischemic stroke had a significantly longer in-hospital stay (18.3±15.5 vs. 6.4±8.0 days; p<0.001), and higher rates of in-hospital mortality (18.0% vs. 3.2%; p<0.001) compared to patients without ischemic stroke. After multivariable adjustment, ischemic stroke remained independently associated with a higher risk of in-hospital mortality with an Odds ratio of 6.5 (95% Confidence Interval: 5.9, 7.1; p<0.001). Also, incidence of peri-interventional stroke increased gradually from 0.03% in 2006 to 0.12% in 2020 (see Figure 1). Conclusion In a contemporary nationwide cohort of patients hospitalized for coronary angiography spanning 15 years, the incidence of ischemic stroke remained low, although a gradual increase from 2006 to 2020 was documented. The occurrence of ischemic stroke was independently associated with a markedly increased risk of in-hospital mortality. These findings might be helpful in evaluating patients undergoing coronary angiography and to reduce the high mortality and morbidity associated with this complication in future. Funding Acknowledgement Type of funding sources: None.