Background: Prior studies reported that only half of stroke patients arrived at emergency departments (ED) via emergency medical services (EMS). We sought to assess predictors of ED mode of arrival and its effects on acute stroke care and inpatient outcomes in a large racial-ethnically diverse cohort. Methods: In 2016, we launched a system-wide standardized telestroke program for 21 certified stroke centers. Non-cancelled stroke alerts included those patients who were potential candidates for further workup for acute ischemic stroke treatment. This study cohort included non-cancelled stroke alerts seen by Telestroke in 2021. Assessment included demographics, ED arrival mode , initial NIH Stroke Scale (NIHSS), neuroimaging results, IV thrombolytic, door-to-needle (DTN) time, large vessel occlusion (LVO), thrombectomy referral, hospital length of stay and discharge disposition. Clustered logistic regression was used to evaluate ED arrival mode’s effects on short-term outcomes. Results: Of the 7744 stroke alerts seen by Telestroke in 2021, 3264 (42.2%) were non-canceled. Among these, 2014 (61.7%) were in the early window (0-4.5 hours from last seen well). More of those arriving in the early window came via EMS compared to those seen in the extended window [1625 (80.7%) versus 729 (58.3%) respectively]. Among non-canceled ED stroke alerts, compared to patients who arrived via EMS, walk-in patients were younger, more Hispanic, had lower initial NIHSS scores, longer times for ED to contact Telestroke, slower DTN times, but less mortality [Table]. In multivariate analysis, walk-in patients were less likely to have a DTN time within 30 minutes (OR=0.37, 95% CI 0.25-0.34; p=<0.001). Conclusions: In our cohort, there were several differences between walk-in patients and those who arrived via EMS. Further research is needed to understand these differences, the reasons for choosing walk-in, and whether ED mode of arrival affects clinical outcomes.