Context: There is substantial hospital-level variation in use of tissue plasminogen activator (tPA) for treatment of acute ischemic stroke. Telestroke services can bring neurologic expertise to hospitals with fewer resources.Objective: To determine whether implementation of a telestroke intervention in a large integrated health system would lead to increased tPA utilization and would change rates of hemorrhagic complications.Design: A stepped-wedge cluster randomized trial of 11 community hospitals connected to 2 tertiary care centers via telestroke, implemented at each hospital incrementally during a 1-year period. We examined pre-and postimplementation data from July 2013 through January 2015. A 2-level mixed-effects logistic regression model accounted for the staggered rollout.Main Outcome Measures: Receipt of tPA. Secondary outcome was the rate of significant hemorrhagic complications.Results: Of the 2657 patients, demographic and clinical characteristics were similar in pre-and postintervention cohorts. Utilization of tPA increased from 6.3% before the intervention to 10.9% after the intervention, without a significant change in complication rates. Postintervention patients were more likely to receive tPA than were preintervention patients (odds ratio = 2.0; 95% confidence interval = 1.2-3.4). Before implementation, 8 of the 10 community hospitals were significantly less likely to administer tPA than the highest-volume tertiary care center; however, after implementation, 9 of the 10 were at least as likely to administer tPA as the highest-volume center.Conclusion: Telestroke implementation in a regional integrated health system was safe and effective. Community hospitals' rates of tPA utilization quickly increased and were similar to the largest-volume tertiary care center.