Background Safe Implementation of Thrombolysis in Stroke-Non-European Union World was a multinational, prospective, open, monitored, observational study of intravenous alteplase as thrombolytic therapy in clinical practice. Safe Implementation of Thrombolysis in Stroke-Non-European Union World was required to assess the safety of alteplase in an Asian population by comparison with results from the European Safe Implementation of Thrombolysis in Stroke-Monitoring Study and pooled results from randomized controlled trials. Aims and/or hypothesis To evaluate the efficacy and safety of intravenous alteplase (0.9 mg/kg) as thrombolytic therapy within three-hours of onset of acute ischaemic stroke in an Asian population. Methods The 591 patients included were treated at 48 centers in four countries (South Korea, China, India, and Singapore) between 2006 and 2008. Primary outcomes were symptomatic (deterioration in National Institutes of Health Stroke Scale score >= 4 or death within the first 24 h) intracerebral haemorrhage type 2 22-36 h after the thrombolysis and mortality at three-month follow-up. The secondary outcome was functional independence (modified Rankin Scale score 0-2) at three-months. Results were compared with those from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (n = 6483) and pooled results of patients (n = 415) who received intravenous alteplase (0.9 mg/kg) zero-to three-hours from onset of stroke symptoms in four randomized controlled trials (National Institute of Neurological Disorders and Stroke A and B, Altephase Thrombolysis for Acute Noninterventional Therapy in Ischaemic Stroke, and European Cooperative Acute Stroke Study II). Results Results are presented as Safe Implementation of Thrombolysis in Stroke-Non-European Union World vs. Safe Implementation of Thrombolysis in Stroke-Monitoring Study vs. pooled randomized controlled trials. Median age was 64 vs. 68 vs. 70 years, National Institutes of Health Stroke Scale score at baseline was 12 vs. 12 vs. 13, time from stroke onset to treatment was 130 vs. 140 vs. 135 mins, and females were 36.4% vs. 39.8% vs. 41.2%. Main outcomes (proportion of patients and 95% confidence intervals) were symptomatic intracerebral haemorrhage: 1.9% (1.1-3.3) vs. 1.7% (1.4-2.0) vs. 3.1% (1.8-5.3); mortality: 10.2% (8.0-12.9) vs. 11.3% (10.5-12.1) vs. 16.4% (13.1-20.3); and functional independence: 62.5% (58.5-66.4) vs. 54.8% (53.5-56.0) vs. 50.1% (45.3-54.9) at three-months. Adjusted odds ratio (95% confidence intervals) between Safe Implementation of Thrombolysis in Stroke-Non-European Union World and Safe Implementation of Thrombolysis in Stroke-Monitoring Study, and between Safe Implementation of Thrombolysis in Stroke-Non-European Union World and the pooled trials were 1.83 (0.89-3.77; P = 0.1156) and 0.63 (0.19-2.07; P = 0.4470) for symptomatic intracerebral haemorrhage, 0.90 (0.64-1.25; P = 0.5092) and 0.93 (0.52-1.64; P = 0.7915) for mortality at three-months, and 1.57 (1.25-1.96; P < 0.0001) and 1.35 (0.91-2.00; P = 0.1325) for functional independence. Conclusions These data demonstrate the safety and efficacy of the standard dose of intravenous alteplase (0.9 mg/kg) in an Asian population, as previously observed in the European population studied in Safe Implementation of Thrombolysis in Stroke-Monitoring Study and the populations in pooled randomized controlled trials, when used in routine clinical practice within three-hours of stroke onset. The findings should encourage wider use of thrombolytic therapy in Asian countries for suitable patients treated in stroke centers.