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Background: Few data exist on acute stroke treatment in patients with pre-existing disability (PD) since they are usually excluded from clinical trials. A recent trial of mobile stroke units (MSUs) demonstrated faster treatment and improved outcomes, and included PD patients., Aim: To determine outcomes with tissue plasminogen activator (tPA), and benefit of MSU versus management by emergency medical services (EMS), for PD patients., Methods: Primary outcomes were utility-weighted modified Rankin Scale (uw-mRS). Linear and logistic regression models compared outcomes in patients with versus without PD, and PD patients treated by MSU versus standard management by EMS. Time metrics, safety, quality of life, and health-care utilization were compared., Results: Of the 1047 tPA-eligible ischemic stroke patients, 254 were with PD (baseline mRS 2-5) and 793 were without PD (baseline mRS 0-1). Although PD patients had worse 90-day uw-mRS, higher mortality, more health-care utilization, and worse quality of life than non-disabled patients, 53% returned to at least their baseline mRS, those treated faster had better outcome, and there was no increased bleeding risk. Comparing PD patients treated by MSU versus EMS, 90-day uw-mRS was 0.42 versus 0.36 (p = 0.07) and 57% versus 46% returned to at least their baseline mRS. There was no interaction between disability status and MSU versus EMS group assignment (p = 0.67) for 90-day uw-mRS., Conclusion: PD did not prevent the benefit of faster treatment with tPA in the BEST-MSU study. Our data support inclusion of PD patients in the MSU management paradigm., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J.C. Grotta has received grants from Patient-Centered Outcomes Research Institute (PCORI), NIH, Genentech, CSL Behring, and Chiesi; is a consultant for Frazer, advison the scientific advisory board for Haemonetics and Acticor, and on the DSMB for Prolong Pharma. J.L. Saver receives contracted hourly payments from Bayer, Biogen, Roche, Genentech, Medtronic, Novo Nordisk, and Occlutech for service on clinical trial steering committees and DSMBs. The remaining authors have no disclosures.