ObjectivesTo assess potential increases in intravenous thrombolysis (IVT) rates given particular interventions in the stroke care pathway.DesignSimulation modelling was used to compare the performance of the current pathway, best practices based on literature review and an optimised model.SettingFour hospitals located in the North of the Netherlands, as part of a centralised organisational model.ParticipantsIschaemic stroke patients prospectively ascertained from February to August 2010.InterventionThe interventions investigated included efforts aimed at patient response and mode of referral, prehospital triage and intrahospital delays.Primary and secondary outcome measuresThe primary outcome measure was thrombolysis utilisation. Secondary measures were onset-treatment time (OTT) and the proportion of patients with excellent functional outcome (modified Rankin scale (mRS) 0–1) at 90 days.ResultsOf 280 patients with ischaemic stroke, 125 (44.6%) arrived at the hospital within 4.5 hours, and 61 (21.8%) received IVT. The largest improvements in IVT treatment rates, OTT and the proportion of patients with mRS scores of 0–1 can be expected when patient response is limited to 15 min (IVT rate +5.8%; OTT −6 min; excellent mRS scores +0.2%), door-to-needle time to 20 min (IVT rate +4.8%; OTT −28 min; excellent mRS scores+3.2%) and 911 calls are increased to 60% (IVT rate +2.9%; OTT −2 min; excellent mRS scores+0.2%). The combined implementation of all potential best practices could increase IVT rates by 19.7% and reduce OTT by 56 min.ConclusionsImproving IVT rates to well above 30% appears possible if all known best practices are implemented.