BACKGROUND AND AIMS: The short time window is frequently cited as the main reason for exclusion of intravenous tissue plasminogen activator (tPA) in acute stroke. Identifying and circumventing barriers to thrombolysis other than time could increase the frequency of treatment. The goal of this study was to identify whether the rate of treatment with tPA would increase if time window was not an obstacle to treatment. METHODS: In four hospitals we prospectively recorded the rate of tPA use in consecutive patients admitted with acute ischemic stroke and in those admitted within 3 hours, the reasons why thrombolysis was not given, and the potential gain in the rate of tPA use if all patients had been admitted within 3 hours considering all exclusion criteria other than time. RESULTS: We recruited 486 patients (258 men; mean age, 70.4 +/- 13.5 years), of whom 154 (31.7%) were admitted within 3 hours. The time of stroke onset was unknown in 28 (5.8%). The rate of tPA use was 11.1% in the whole study population and 35.1% in those admitted within 3 hours. In 'eligible' patients, TIA in 33 patients (21.4%), age >80 years in 27 (17.5%), mild stroke in 27 (17.5%), rapidly recovering stroke in 9 (5.8%), a too long door-to-needle time in 8 (5.2%), and severe hypertension in 5 (3.2%) were the main reasons for not to treat. Two patients were not treated despite the absence of documented reasons. If all patients had hypothetically been admitted within 3 hours, the rate of tPA use would have increased from 11.1% up to 27.9% of the whole population and up to 37.4% if aged patients and those with no documented reasons or with a rapidly recovering stroke had also been considered for treatment. CONCLUSIONS: Delayed presentation to hospital is the main factor limiting the use of thrombolysis in acute stroke, but additional patients would be treated if those with no contraindication, advanced age or rapidly recovering stroke were considered as eligible.