Abstract Intravenous tissue plasminogen activator (tPA) has been licensed in Australia for thrombolysis in selected patients with acute ischaemic stroke since 2003. The use of tPA is low but is increasing across Australia and national audits indicate efficacy and safety outcomes equivalent to international benchmarks. Implementing tPA therapy in clinical practice is, however, challenging and requires a coordinated multidisciplinary approach to acute stroke care across prehospital, emergency department and inpatient care sectors. Stroke care units are an essential ingredient underpinning safe implementation of stroke thrombolysis. Support systems such as care pathways, therapy delivery protocols, and thrombolysis-experienced multidisciplinary care teams are also important enablers. Where delivery of stroke thrombolysis is being planned, health systems need to be re-configured to provide these important elements. This consensus statement provides a review of the evidence for, and implementation of, tPA in acute ischaemic stroke with specific reference to the Australian health-care system.