Background: Therapeutic benefit/risk from thrombolysis in acute ischaemic stroke declines sharply with delayed initiation of treatment (OTT), the window closing around 4.5hours from stroke onset. Recent overview data have indicated that risk/benefit from alteplase initiation within approximately 3 hours from stroke onset does not deteriorate with advancing age. However, some clinicians speculate that the gradient of the OTT-benefit relation may be steeper in the elderly. Methods: We assessed the relation between OTT and the effect of thrombolysis among 3063 registry patients with reliable surrogate information on OTT. After replicating the pooled thrombolysis-trial analysis findings among younger patients, we analysed the subgroup of patients aged >80 years. We matched non-thrombolysed patients (control; n=245) having a recorded OTT of the investigational drug to thrombolysed patients (treatment; n=352) having a recorded OTT of alteplase ≥1h and ≤3.5h, using data from neuroprotectant trials held within the Virtual International Stroke Trials Archive (VISTA). Results: Adjusted for baseline NIHSS and age, the OR for improved 90 day outcome with thrombolysis measured by the modified Rankin Score was 1.46 (95% CI 1.08-1.97, p=0.001). There was no significant interaction with OTT (p=0.465), but CIs were wide. The decay in benefit with increasing OTT appears little different to that established for younger patients. Conclusion: Evidence from multiple sources is consistent. We conclude that thrombolysis is effective and safe in very elderly stroke patients until at least 3.5h after stroke onset.