The benefits of intravenous tissue-plasminogen activator (tPA) in acute ischemic stroke are time-dependent. Emergency medical services (EMS) hospital prenotification of an incoming patient with potential stroke may provide a means of reducing evaluation and treatment times and improving treatment rates; yet, available data are limited. We examined 371 988 patients with acute ischemic stroke transported by EMS and enrolled in Get With The Guidelines-Stroke from April 1, 2003, to March 31, 2011. Prenotification occurred in 249 197 (67.0%) of EMS-transported patients. Among eligible patients arriving by 2 hours, patients with EMS prenotification were more likely to be treated with tPA within 3 hours (82.8% versus 79.2%, absolute difference +3.5%, P<0.0001, the National Institutes of Health Stroke Scale-documented cohort; 73.0% versus 64.0%, absolute difference +9.0%, P<0.0001, overall cohort). Patients with EMS prenotification had shorter door-to-imaging times (26 minutes versus 31 minutes, P<0.0001), shorter door-to-needle times (78 minutes versus 80 minutes, P<0.0001), and shorter symptom onset-to-needle times (141 minutes versus 145 minutes, P<0.0001). In multivariable and modified Poisson regression analyses accounting for the clustering of patients within hospitals, use of EMS prenotification was independently associated with greater likelihood of door-to-imaging times ≤25 minutes, door-to-needle times for tPA ≤60 minutes, onset-to-needle times ≤120 minutes, and tPA use within 3 hours. EMS hospital prenotification is associated with improved evaluation, timelier stroke treatment, and more eligible patients treated with tPA. These results support the need for initiatives targeted at increasing EMS prenotification rates as a mechanism from improving quality of care and outcomes in stroke.