Objectives <p>A distributional cost-effectiveness analysis (DCEA) was conducted to evaluate how alteplase for acute ischemic stroke affected overall health and disparities in the USA.</p> Methods <p>Using an existing, published, cost-effectiveness analysis, a DCEA was developed from a US payer perspective. The population was divided into 25 equity-relevant subgroups based on race and ethnicity (5 census-based groups), and county-level social vulnerability index (quintiles). Inputs for stroke outcomes, incidence and alteplase utilization varied across subgroups. Opportunity costs were estimated by converting total spend on alteplase into quality-adjusted life-years (QALYs) using an equal distribution across subgroups. Various scenarios explored the impact of health system changes to improve stroke care access.</p> Results <p>Alteplase treatment resulted in larger relative QALY gains in more vulnerable versus less vulnerable subgroups owing to increased acute ischemic stroke incidence and lower receipt of thrombolysis. Using an opportunity cost threshold of US$150,000/QALY, alteplase was estimated to improve social welfare by increasing population health (45,606 QALYs gained) and reducing existing overall US inequities by 0.0001% annually. Results were robust across all levels of population inequality aversion and alternate opportunity cost thresholds. Health system scenarios that reduced care gaps promoted additional reductions in existing inequalities, because more patients with lower baseline health were eligible for treatment.</p> Conclusions <p>Under current treatment patterns, this DCEA demonstrated that alteplase for acute ischemic stroke increased population health and improved health equity. It is critical to address existing care gaps to enable equitable access to alteplase across race, ethnicity and geography.</p>