Background: Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is licensed for use within 3 h of acute ischaemic stroke. The less the delay to treatment, the more likely it is to be effective. Aims: To assess the effectiveness of interventions designed to overcome barriers to rapid administration of thrombolytic therapy. Design: Systematic review of previous clinical studies. Methods: We searched for studies that evaluated the effect of an intervention to reduce delays to administration of rt-PA. We searched MEDLINE, EMBASE, the trials register of the Cochrane Stroke Group, and the Cochrane Controlled Trials Register. We sought randomized and non-randomized controlled trials, before-and-after studies, interrupted time series, and observational studies. Results: We identified 10 non-randomized studies that evaluated interventions that could speed up admission to hospital and administration of rt-PA. The types of interventions included: (a) education programmes for the public to improve their knowledge about symptoms of acute stroke; (b) training programmes for paramedical staff to improve their accuracy of stroke diagnosis and hasten transport of the patient to hospital; (c) helicopter transfer of patients to hospital; (d) training programmes in acute stroke therapy for emergency department staff; and (e) re-organization of in-hospital systems to streamline acute stroke care. Several programmes were multifaceted interventions. Discussion: We identified important areas that could be targets for interventions to improve the efficiency of delivering thrombolysis for acute stroke. Multifaceted programmes might be more likely to be successful in reducing delays to therapy.