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Background: After endovascular therapy (EVT) became standard of care for acute ischemic stroke (AIS) in 2015, emergency medical services (EMS) in 3 urban southeast Florida counties modified their transport protocols for suspected AIS. In 2015, Broward (BC) and Palm Beach counties (PBC) phased in EMS transport of all stroke alerts to state-attested comprehensive stroke centers (CSC). Miami-Dade (MDC) adopted a severity-based protocol.Methods: The impact of EMS policy changes was assessed using the AHA Get with the Guidelines-Stroke data prospectively collected for the Florida-Puerto Rico Stroke Registry involving 35,794 AIS cases in the 3 counties with 27 CSC between 2010 and 2016.Results: The percent of patients transported directly by EMS from scene to CSCs in BC and PBC rose from 34% and 13% during 2010, to 97% and 86%, respectively, in 2016 (p=0.002). In MDC, it increased from 62% to 77%. In 2016, the percentage of AIS patients that presented to CSC as transfers from primary stroke centers (PSC) was 5% in BC, 8% in PBC, and 12% in MDC. Of all patients receiving IV tPA in 2016, 81% were transported by EMS and 87 % of IV tPA treatment was administered in a CSC. From 2010 to 2016, IV tPA treatment increased from 8% to 18% in CSC vs. 8% to 12% in PSC (p=0.41). By 2016 the mean door to needle time was 13 min shorter in CSCs (p<0.001). Mean interval from symptom onset to IV tPA (OTT) decreased to 112 min in CSC vs. 125 min in PSC (p=0.047) and 19% of patients at CSCs had an OTT in the “golden hour” compared to 11% at PSCs. In 2016 the mean onset to arrival in patients transferred from PSC to CSC for EVT was 109 min longer than in those directly transported to CSC. The percentage of patients receiving EVT increased overall to 6%, with 9 CSC reporting greater than 10% EVT, 5 CSC greater than 15%, and 2 greater than 20% EVT for all AIS cases.Conclusion: Modifying EMS policies to transport most suspected AIS patients directly to CSCs was associated with higher rates of IV tPA treatment, shorter intervals to IV tPA after symptom onset, faster arrival times for EVT evaluation and higher rates of EVT compared to patients triaged to PSCs. Based on these findings, directly transporting suspected AIS patients to CSC may be a successful strategy to expedite stroke care interventions in urban centers with high CSC density.