The Stroke Therapy Academic Industry Roundtable (STAIR) updated preclinical recommendations aim to improve the quality and relevance of preclinical studies for acute stroke therapies. The original 1999 recommendations, while reasonable, were not widely followed or rigorously validated. The updated guidelines emphasize the importance of reproducibly defining dose-response and time windows with both histological and functional outcomes in multiple animal species, along with appropriate physiological monitoring. Key recommendations include eliminating bias, a priori defining inclusion/exclusion criteria, performing power and sample size calculations, and disclosing conflicts of interest. Studies should also be conducted in females, aged animals, and those with comorbid conditions. Clinically relevant biomarkers should be used in animal studies. The updated recommendations also highlight the need for studies in multiple species, including rodents and gyrencephalic primates, to ensure broader applicability. They stress the importance of reproducibility, with results from one laboratory needing to be replicated in another before advancing to clinical trials. The guidelines also emphasize the need for appropriate outcome measures, including both histological and behavioral assessments, and the importance of physiological monitoring. The recommendations aim to enhance the chances of successful clinical translation by ensuring rigorous and unbiased preclinical testing. The updated STAIR recommendations are intended to provide a framework for improving the quality of preclinical studies and to guide future research in stroke therapy.The Stroke Therapy Academic Industry Roundtable (STAIR) updated preclinical recommendations aim to improve the quality and relevance of preclinical studies for acute stroke therapies. The original 1999 recommendations, while reasonable, were not widely followed or rigorously validated. The updated guidelines emphasize the importance of reproducibly defining dose-response and time windows with both histological and functional outcomes in multiple animal species, along with appropriate physiological monitoring. Key recommendations include eliminating bias, a priori defining inclusion/exclusion criteria, performing power and sample size calculations, and disclosing conflicts of interest. Studies should also be conducted in females, aged animals, and those with comorbid conditions. Clinically relevant biomarkers should be used in animal studies. The updated recommendations also highlight the need for studies in multiple species, including rodents and gyrencephalic primates, to ensure broader applicability. They stress the importance of reproducibility, with results from one laboratory needing to be replicated in another before advancing to clinical trials. The guidelines also emphasize the need for appropriate outcome measures, including both histological and behavioral assessments, and the importance of physiological monitoring. The recommendations aim to enhance the chances of successful clinical translation by ensuring rigorous and unbiased preclinical testing. The updated STAIR recommendations are intended to provide a framework for improving the quality of preclinical studies and to guide future research in stroke therapy.