Patients in rural communities lack access to acute stroke therapies. Rapid administration of thrombolytic therapy increases the likelihood of a favorable outcome in ischemic stroke. We aimed to detail the safety, feasibility, and treatment times of thrombolytic therapy with a web-based telestroke system. At the Medical College of Georgia, we have developed a telestroke system (Remote Evaluation of Acute IsCHemic Stroke; REACH) in which emergency physicians in surrounding counties may consult stroke specialists at our institution. The web-based system allows the stroke consultant to obtain history, examine the patient with live video, and review computed tomography. A recommendation is made regarding the administration of tissue plasminogen activator (tPA) before patient transport to the tertiary medical center. A systematic review of the literature was conducted regarding the use of tPA in academic and community hospitals. Symptomatic hemorrhagic transformation and stroke onset-to-treatment times were compared between the REACH network and other stroke care delivery systems. Between February 2003 and March 2006, 50 patients were treated with intravenous tPA using the REACH telestroke system. There was one (2%) symptomatic hemorrhage. The mean onset-to-treatment time was 127.6 min (95% confidence interval 117.1-138.0) using REACH compared with 145.9 min (95% confidence interval 126.9-164.9) in our Emergency Department and 147.8 min in other published systems. REACH, a web-based telestroke system, facilitates the safe administration of thrombolytic therapy to patients within rural communities suffering an acute ischemic stroke.