Background and purpose In 1995 intravenous recombinant tissue plasminogen activator (IVRTPA) was the first reperfusion therapy to be approved in patients with acute ischaemic stroke (AIS). The significance and impact of IVRTPA in times of modern endovascular stroke treatment (EST) were analysed in a German academic stroke centre. Methods A retrospective observational cohort analysis of 1034 patients with suspected AIS presenting at the emergency department in 2014 was performed. Patients were evaluated for baseline characteristics, reperfusion procedures, IVRTPA eligibility, clinical outcome, symptomatic intracranial haemorrhage (sICH) and mortality. Data acquisition was part of an investigator‐initiated, prospective and blinded end‐point registry. Results In 718 (69%) patients the diagnosis of symptomatic AIS was confirmed. 419 (58%) patients presented within 4.5 h of symptom onset and of those 260 (62%) received reperfusion therapy (IVRTPA alone, n = 183; combination or bridging therapy, n = 60; EST alone, n = 17). Subtracting cases with absolute contraindications for IVRTPA resulted in an effective thrombolysis rate of 82%. sICH occurred in two patients treated with IVRTPA alone (1.1%). The median door‐to‐needle interval was 30 min. Fifty (17%) non‐EST eligible AIS patients presenting within 4.5 h without absolute contraindications did not receive IVRTPA mainly due to mild or regressive symptoms. Most of these untreated IVRTPA eligible patients (82%) were discharged with a good clinical outcome (modified Rankin Scale ≤ 2). Conclusions Intravenous recombinant tissue plasminogen activator remains the most frequently applied reperfusion therapy in AIS patients presenting within 4.5 h of onset in a tertiary stroke centre. An effective thrombolysis rate of over 80% can be achieved without increased rates of sICH.