Background: Intravenous thrombolysis is an effective emergency treatment for acute ischaemic stroke for patients meeting specific criteria. Approximately 12% of eligible patients in England, Wales and Northern Ireland received thrombolysis in the first quarter of 2013, yet as many as 15% are eligible to receive treatment. Suboptimal use of thrombolysis may have been largely attributable to structural factors; however, with the widespread implementation of 24/7 hyper acute stroke services, continuing variation is likely to reflect differences in clinical decision-making, in particular the influence of ambiguous areas within the guidelines, licensing criteria and research evidence. Clinicians' perceptions about thrombolysis may now exert a greater influence on treatment rates than structural/service factors. This research seeks to elucidate factors influencing thrombolysis decision-making by using patient vignettes to identify (1) patient-related and clinician-related factors that may help to explain variation in treatment and (2) associated trade-offs in decisionmaking based on the interplay of critical factors. Methods/analysis: A discrete choice experiment (DCE) will be conducted to better understand how clinicians make decisions about whether or not to offer thrombolysis to patients with acute ischaemic stroke. To inform the design, exploratory work will be undertaken to ensure that (1) all potentially influential factors are considered for inclusion; and (2) to gain insights into the 'grey areas' of patient factors. A fractional factorial design will be used to combine levels of patient factors in vignettes, which will be presented to clinicians to allow estimation of the variable effects on decisions to offer thrombolysis. Ethics and dissemination: Ethical approval for this study was obtained from the Newcastle University Research Ethics Committee. The results will be disseminated in peer review publications and at national conferences. Findings will be translated into continuing professional development activities and will support implementation of a computerised decision aid for thrombolysis (COMPASS) in acute stroke care.