•Modern stroke Treatments (endovascular thrombectomy and intravenous thrombolysis) are cost-effective.•Moving from more traditional to modern stroke treatments can reduce mortality and disability at affordable cost.•Results of this study could be leveraged by including effects of preventive policies and rehabilitation. Stroke is the most common cause of disability in high-income countries. Several countries offer a limited range of advanced treatments with implications for outcomes, disability and costs. This study estimates the burden of disability that could have been avoided through the transition from traditional (no intravenous thrombolytic therapy (IVT), or endovascular thrombectomy (EVT)) to modern stroke treatments (treatment in stroke units, IVT and EVT). We perform a cost-effectiveness analysis comparing best practice with traditional stroke care, using Greece as a case study. A Markov model was used to calculate costs and Quality Adjusted Life Years (QALYs) for each treatment strategy, using a lifetime horizon. Data for model inputs were derived from meta-analyses of trials, and national and international cost databases. Sensitivity analyses were also performed to address potential uncertainty and test the robustness of the findings. Incremental effectiveness comprised 0.22 QALYs per patient and year. Best practice was cost-effective for more than 90% of all iterations (ICER for the baseline scenario: €2,109.25/QALY). Sensitivity analysis demonstrated that the findings remain robust. Considering the stroke incidence in Greece, the annual additional cost to implement best practice was calculated to be between 0.07%-0.15% of the total health expenditure. Best practice stroke treatment was cost-effective and affordable in a case study based on Greece. The results could be leveraged by including effects of preventive policies and rehabilitation. They also highlight the importance of adopting modern treatment strategies from a cost-effectiveness perspective, apart from the improved clinical outcomes.