Intravenous recombinant tissue plasminogen activator is a highly effective treatment for acute ischemic stroke, but routine provision is challenging. We compared the activity, safety and response times of five service configurations: local services, redirection of selected or all suspected stroke patients by emergency medical services (EMS) to stroke centers and the use of telemedicine with and without secondary transfer to a stroke center. In total, 59 relevant service descriptions were identified. Pooled treatment rates (mean +/- standard deviation [SD]) per 100 confirmed stroke patients were: local service design, 2.5 +/- 2.5 (n = 21417); EMS redirection of only patients potentially eligible for thrombolysis, 3.9 +/- 1.2 (n = 1872); EMS redirection of all suspected stroke patients, 3.8 +/- 1.1 (n = 5427); telemedicine with secondary transfer, 6.9 (no pooled SD; n = 749); and telemedicine without secondary transfer, 3.4 (no pooled SD; n = 6610). A comprehensive stroke patient register was completed for only five regional collaborations, resulting in pooled ischemic stroke treatment rates of 5.7 (95% confidence interval: 4.6-6.9; n = 7815) compared with 3.1 (95% confidence interval: 2.1-4.1; n = 31411) for local services. Pooled symptomatic hemorrhage rates were similar for all service designs (range: 3.9-5.1%). Average door-needle times exceeded 60 min in most studies. We conclude that regional collaborations achieve higher rates of thrombolysis than local services working in isolation. Stroke services should continue to publish thrombolysis activity and safety data in a recommended format in order to determine the most suitable configuration for different settings.