The use of tissue-type plasminogen activator (t-PA) in ischaemic stroke outside of experienced stroke centres remains controversial. The aim of this study was to present the initial experience with t-PA in patients with ischaemic stroke at an institution with no prior experience in i.v. stroke thrombolysis and to compare results to published reports. Prospective audit of 888 patients with consecutive stroke and transient ischaemic attack admitted to a 426-bed tertiary referral hospital from March 2003 to October 2005. Main outcome measures were treatment rate, exclusion criteria, protocol violations, intracerebral haemorrhage, disability (modified Rankin scale) and mortality at 3 months. Over the study period, 72 patients received t-PA (11% of ischaemic strokes). The main reason for exclusion was presentation beyond 3 h of onset (44%); if all eligible patients had arrived within 3 h, treatment rate was estimated at 32.5%. Protocol violations occurred in 15 (21%) patients. There were seven (10%) asymptomatic intracerebral haemorrhage and one (1%) non-fatal symptomatic intracerebral haemorrhage. At 3 months, 37% had achieved excellent recovery (modified Rankin scale 0-1) and seven (10%) had died. The delivery and outcomes associated with the use of t-PA were comparable to the results of the National Institute of Neurological Disorders and Stroke trial and meta-analysis of open-labelled studies. With appropriate infrastructure and protocols, previously inexperienced tertiary referral centres can replicate the experience and outcome measures reported by clinical trials of t-PA in patients with stroke.