Objectives: To examine whether thrombolysis care metrics have improved in all races and ethnicities with the launch and advance of Target: Stroke (TS) national quality initiatives. Methods: This cohort study included patients presenting to Get With The Guidelines (GWTG)-Stroke participating hospitals within 4.5 hours of ischemic stroke onset from 2003 to 2021. Thrombolysis rates and speed of treatment during TS phase I (2010-2013), II (2014-2018), and III (2019-2021) were compared with the pre-TS period (2003-2009). Results: Among all the patients with ischemic stroke, Asian, Black, and Hispanic individuals, compared with White, were significantly more likely to present after the 4.5-hour thrombolysis treatment window (Figure/Panel A and B). Among the 1,182,182 patients arriving within 4.5 hours, 33,375 were Asian, 180,315 Black, 86,831 Hispanic, and 881,661 White. Unadjusted rates of thrombolysis treatment increased in all race-ethnic groups from 2003 to 2021 (Figure/Panel C) with no significant disparities. Disparities were evident in adjusted analyses (Figure/Panel D) and persisted in TS:III when, compared with White patients, Asian, Black, and Hispanic patients had significantly lower odds of receiving thrombolysis (0.85, 0.76, and 0.86) (all p values<0.05). Door-to-needle (DTN) times significantly improved in all race-ethnic groups during TS (Figure/Panel E). However, compared with White patients, Asian, Black, and Hispanic patients had significantly lower odds of DTN≤60 minutes (Figure/Panel F) which persisted in TS:III (adjusted OR 0.91, 0.78, and 0.87) (all p values<0.05). Conclusion: Target: Stroke was associated with substantial improvement in thrombolysis frequency and timeliness for all races and ethnicities, but disparities persisted after risk adjustment. Further stroke system of care and health equity interventions should focus on early hospital arrival and quality reporting of risk-adjusted care metrics by race-ethnicity.