BACKGROUND: This study aims to evaluate temporal trends of advanced treatments and related clinical outcomes of ischemic stroke through a decade-long trend analysis, using data from a comprehensive, national, multicenter registry. We also seek to identify areas in need of improvement. METHODS AND RESULTS: This analysis involved patients with ischemic stroke or transient ischemic attack registered prospectively in the CRCS-K-NIH (Clinical Research Center for Stroke in Korea-National Institute of Health) registry between 2011 and 2020. We examined temporal trends in risk factors, pathogenetic subtypes, acute management strategies, and outcomes for up to 1 year following a stroke. Generalized linear mixed models were used to account for center clustering. The average age of 77 662 patients increased 2.2 years in men and 2.4 years in women over the 10-year follow-up. Notably, in-hospital neurological deterioration, 3-month and 1-year mortality rate, and cumulative incidence of recurrent stroke within 1-year decreased over time after adjustments for age, sex, and initial stroke severity ( CONCLUSIONS: This study points to a reduction in death and risk of recurrent stroke over the past decade, paralleling enhancement in acute and preventive stroke management. Nevertheless, the decline in the use of intravenous thrombolysis and the lack of improvement in functional outcomes following stroke are concerning trends that warrant thorough investigation.