To investigate the safety and efficacy of stroke thrombolysis in a local hospital. Historical cohort study. A tertiary hospital in Hong Kong. The outcome of acute ischaemic stroke patients treated with intravenous tissue plasminogen activator between October 2008 and May 2011 was compared to those admitted during the same period who were thrombolysis-eligible, but treated conservatively due to unavailability of the thrombolysis service after-hours. Intravenous tissue plasminogen activator. Primary outcome was functional independence (modified Rankin Scale score of 2 or below) at 3 months. Safety outcomes were symptomatic intracranial haemorrhage and 3-month mortality. Secondary outcomes were hospital length of stay, direct home discharge, and nursing home discharge. A total of 48 thrombolysis and 63 non-thrombolysis patients were identified. Fifty-two percent of the thrombolysis group achieved functional independence compared to 24% of non-thrombolysis group (P=0.003), without significant increase in mortality (15% vs 13%, P=0.51) or symptomatic intracranial haemorrhage (4% vs 2%, P=0.58). Twenty-nine percent of the thrombolysis group patients were discharged home directly, versus 6% of non-thrombolysis group (P<0.001). Mean length of stay was shorter for the thrombolysis group (25 vs 35 days; P=0.034). A similar percentage from each group was discharged to nursing homes. Implementation of the stroke thrombolysis service in Hong Kong appeared safe and efficacious. Patients who received thrombolysis had better outcomes compared to non-thrombolysis cohort. Further studies are needed to investigate the economics of stroke thrombolysis in Hong Kong, which may help to improve funding for provision of this service.