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BACKGROUND The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS A retrospective multicenter cohort study that included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid health region. We compared the characteristics of stroke patients with or without a COVID-19 diagnosis and analyzed the organizational changes in stroke care between the first (February 25 to April 25, 2020) and second wave (July 21 to November 21, 2020). RESULTS A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of 9 patients in both waves. During the second wave, there was a decrease in stroke severity (median NIHSS 5 vs. 6; p=0.000), in-hospital strokes (3% vs. 8.1%), and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.