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Background Thrombolysis treatment varies considerably between in- and out-of-hours services. Aims This improvement initiative aimed to upskill acute stroke unit nurses as stroke thrombolysis response nurses, testing a new model of nursing in readiness for hyperacute stroke unit developments. Methods Three registered nurses were trained to a specialist competency framework. The role was tested over 28 weeks, and times to treatment milestones were measured. Thrombolysed patients from the test period were statistically compared with a matched group using a two-sample t-test in Excel. Qualitative feedback was sought from the stroke team, medical and emergency department colleagues. Findings Median out-of-hours door-to-needle time reduced from 85 to 61.5 minutes. Statistically significant differences were seen in the time to stroke unit admission (p=0.012) and swallow screen (p=0.038). Stroke and emergency department colleagues considered the role essential to out-of-hours thrombolysis treatment. Conclusions The stroke thrombolysis response nurse role reduced variation in treatment and improved timely acute stroke care. This work may inform the development of stroke nursing workforce models.