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Background: To improve stroke care, the Brain Attack Coalition recommended establishing primary stroke center (PSC) and comprehensive stroke center (CSC) certification. Achieving CSC designation requires the ability to provide more complex services. However, it remains unknown whether CSCs have better performance than PSCs for ischemic stroke care. This study compared ischemic stroke care between CSCs and PSCs.Methods: The study included consecutive patients who were admitted to the 134 CSCs and 1047 PSCs participating in Get With The Guidelines (GWTG)-Stroke between January 1, 2013 and December 31, 2015 with a final diagnosis of acute ischemic stroke. Multivariable logistic regression models were generated to examine the association between stroke center certification (CSC vs PSC) and performance measures and outcomes, after adjusting for potential confounders including patient and hospital characteristics.Results: Of the 605,136 patients who were admitted directly from the emergency department, 110,624 were admitted to CSCs and 494,512 to PSCs. CSCs were larger than PSCs (median number of beds 481 vs 263). Performance differences between CSCs vs. PSCs are shown in the table. CSCs and PSCs had comparable overall conformity to the seven performance measures represented by the summary defect-free care measure. CSCs outperformed PSCs in several key measures, especially the use of intravenous tissue plasminogen activator (IV tPA) and intra-arterial thrombectomy (IA-therapy). Compared with patients at PSCs, patients at CSCs were more likely to receive IV tPA in both unadjusted and adjusted models. The door to IV tPA time was shorter at CSCs. Patients at CSCs were more likely to receive IA therapy, with shorter door to IA therapy times. Mortality was higher at CSCs.Conclusions: Stroke care at CSCs exceeded PSCs for many but not all quality measures, particularly timely acute reperfusion therapy. Risk adjusted in-hospital mortality was modestly higher at CSCs.