Background and Purpose— There is evidence that high-volume hospitals may produce better patient outcomes. We aimed to identify whether there were any associations between hospital thrombolysis volume and speed of thrombolysis (tissue-type plasminogen activator [tPA]) administration in patients with ischemic stroke. Methods— Data were drawn from 2 national clinical audits in England: the Stroke Improvement National Audit Program and the 2012 Sentinel Stroke Audit. Hospitals were categorized into 3 groups based on the annualized volume of thrombolysis: 0 to 24, 25 to 49, and ≥50 cases per annum. Arrival-brain scan, onset-tPA, and arrival-tPA times were compared across groups and stratified by onset-arrival time. Multilevel logistic models were used to estimate the odds of receiving tPA within 60 minutes of arrival. Results— Of the 42 024 patients with acute ischemic stroke admitted to 80 hospitals, 4347 received tPA (10.3%). Patients admitted to hospitals with an annual thrombolysis volume of ≥50 cases per annum had median arrival-tPA times that were 28 and 22 minutes shorter than patients admitted to hospitals with volumes of 0 to 24 and 25 to 49, respectively. Onset-tPA times were shorter by 24 to 32 minutes across strata of onset-arrival times. In multivariable analysis, patients admitted to hospitals with a volume of ≥50 cases per annum had 4.33 (2.21–8.50; P <0.0001) the odds of receiving tPA within 60 minutes of arrival. No differences in safety outcomes were observed, with similar 30-day mortality and complication rates across the groups. Conclusions— Hospitals with higher volumes of thrombolysis activity achieve statistically and clinically significant shorter delays in administering tPA to patients after arrival in hospital.