Introduction: Stroke medicine has evolved over time, with changing demographics and improving outcomes. We aimed to evaluate trends in incidence, risk factors, treatment and case fatality of acute ischemic stroke (AIS) in a multiethnic population. Methods: Data was obtained from the Singapore Stroke Registry. 60,325 AIS cases that presented to Singapore’s public hospitals from 2005-16 were studied. Trends were analyzed with Poisson regression, logistic regression and Cox regression. Results: The AIS age-standardized incidence rate has decreased by 11.6% (126.5 to 111.8 per 100,000 person-years from 2005-07 to 2014-16, p < 0.001). This was observed in all gender and ethnic groups except in those younger than 65, which saw a 2.5% increase (51.0 to 52.4 per 100,000 person-years, p = 0.017). In terms of risk factors, hypertension, hyperlipidemia, and atrial fibrillation have increased in prevalence, while history of stroke, ischemic heart disease, diabetes, and smoking have decreased (Figure A). Treatment-wise, thrombolysis utilization rates have increased significantly from 0.8% in 2005-2007 to 6.7% in 2014-2016 (p < 0.001). While atrial fibrillation (AF) has become more prevalent (15.8% to 25.2%, p < 0.001), anticoagulant prescription has not increased by the same magnitude (13.2% to 14.4%, p = 0.014). Case fatality has reduced by 25.6% (8.2% to 6.1%, p < 0.001). Conclusion: In a multi-ethnic population, whilst we found that AIS age-standardized incidence rate has been declining, we demonstrate a temporal trend of changing risk factors. Further research is needed to investigate the causes and implications of these trends, so as to better strategize prevention efforts.