Aim: To describe the United Kingdom (UK) experience with thrombolytic therapy with intravenous alteplase (rt-PA) for stroke, as captured by the Implementation of Thrombolysis in Stroke (SITS) project. Methods: The multinational Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was an observational study to assess the safety and efficacy of thrombolytic therapy, when administered within the first 3 h after onset of ischaemic stroke. SITS-MOST was embedded within the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR), an internet-based, international monitoring registry for auditing the safety and efficacy of routine therapeutic use of thrombolysis in acute ischaemic stroke. We performed an analysis of data contributed to SITS-MOST and SITS-ISTR from UK centres. Results: A total of 614 patients received thrombolysis for stroke between December 2002 and April 2006, 327 were registered to SITS-MOST and 287 to SITS-ISTR. Thirty-one centres treated patients in the UK, of which 23 registered patients in both SITS-MOST and SITS-ISTR and eight solely to SITS-ISTR. The median age from the UK SITS-MOST was identical to the non-UK SITS-MOST register: 68 years (IQR 5975). The majority (96.1) of patients from the UK were treated between 8.00 a.m. and 9.00 p.m., and only 18.4 were treated on weekend days, reflecting the difficulties of maintaining provision of a thrombolytic service out of hours. Median onset-to-treatment-time was 155 min (IQR 130170 min) for the UK, compared to 140 min (IQR 114165 min) for the non-UK SITS-MOST group (P < 0.001). UK SITS-MOST patients at baseline had more severe stroke in comparison with non-UK patients [median NIHSS 14.5 (IQR 919) vs. 12 (IQR 817) (P < 0.001)]. Forty-eight percent of UK patients achieved mRS of 02 (independence), compared to 55 of the non-UK SITS-MOST register. There was no significant difference in symptomatic intracerebral haemorrhage rate in the UK compared with the non-UK SITS-MOST patients [2.5 (95 CI 1.34.8) vs. 1.7 (95 CI 1.42.0) P = 0.28]. In the multivariate analysis, there was no statistically significant difference in any outcome between UK and non-UK SITS-MOST patients. Conclusion: Thrombolytic therapy for stroke has been implemented successfully at a small number of UK stroke centres, with patchy provision throughout the country. The low frequency of treatment outwith office hours suggests deficient infrastructure to support delivery. UK patients tended to be more severely affected at baseline and to be treated later. Outcomes are comparable to those seen at the non-UK SITS centres.