Background: The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program., Methods: We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications., Results: Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event ( P <0.01 for all). In patients with acute ischemic stroke, large improvements were observed for anticoagulation for atrial fibrillation (55.7% in 2003 to 97.2% in 2022), smoking cessation counseling (44.7%-97.8%), dysphagia screening (53.8%-83.5%), thrombolytic treatment for patients arriving by 3.5 hours, treat by 4.5 hours (15.2%-92.9%), door-to-needle time within 60 minutes (19.0%-75.3%), and endovascular door-to-puncture time within 90 minutes (54.7%-62.8%). Similar improvements were also observed for measures relevant to patients with subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack. Multivariable analysis showed that there was a sustained increase in odds of receiving each performance measure over time, independent of patient and hospital characteristics for each type of cerebrovascular event. After risk adjustment, there were temporal trends that patients were less likely to be discharged to a skilled nursing facility, and, for ischemic stroke only, more likely to be discharged directly home., Conclusions: During the first 20 years, Get With The Guidelines-Stroke participation was associated with sustained improvement in evidence-based care and outcomes for patients with stroke and transient ischemic attack in the United States., Competing Interests: Dr Xian reports research funding from the American Heart Association and the National Institute on Aging (R01AG062770 and R01AG066672);grants from Daiichi Sankyo Company; grants from Genentech; travel support from Boehringer Ingelheim; and grants from Janssen Pharmaceuticals Inc. Dr Smith reports service as an editor for the Stroke journal. Dr Saver reports consulting fees for advising on rigorous and safe clinical trial design and conduct from Abbott, Acticor, Aeromics, Amgen, Argenica, Astrocyte, Bayer, Biogen, Boehringer Ingelheim, BrainsGate, BrainQ, CSL Behring, Filterlex, Genentech, Johnson&Johnson, MindRhythm, Medtronic, NeuroMerit, Neuronics, Novo Nordisk, Occlutech, Phenox, Phillips, QuantalX, Rapid Medical, Roche, and Stream Biomedical; compensation from MIVI Neuroscience for data and safety monitoring services; and stock options in Rapid Medical, Neuronics Medical, and MindRhythm. Dr Sheth reports grant support from National Institutes of Health, American Heart Association, and Hyperfine; consulting from Astrocyte, Rhaeos, Cerevasc, Bexorg, Sense and Philips Data and Safety Monitoring Board; and patent with Alva; and compensation from Certus for consultant services; stock options in BrainQ. Dr Messé reports personal compensation from Novo Nordisk for work on the Clinical Event Committee for ONWARDS and Zeus Trials; Terumo for work on the Subject Selection Committee for the RelayBranch Trial; WL Gore for work on the Data Safety Monitoring Committee for the GORE CARDIOFORM Septal Occluder Post Marketing Trial; and Conformal Medical for work on the Clinical Event Committee for work on the Conformal left atrial appendage closure trial. He also reports equity in Neuralert Technologies. Dr Schwamm reports consulting for Genentech (member of TIMELESS steering committee NCT03785678), LifeImage, Penumbra (DSMB MIND NCT03342664), Medtronic (co-PI Stroke AF NCT02700945, advise on stroke prevention), grant funding from NINDS (PI, U24NS107243; Co-I, R01NS111952) and PCORI (R-1609-35995), and serves as member board of directors for the American Heart Association. Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. The other authors report no conflicts.