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Background and Purpose— Shorter delays between symptom onset and treatment translate into better outcomes after ischemic stroke thrombolysis. There are considerable intercenter variations in treatment delivery. We analyzed the trends of door-to-needle times (DNTs) in the Safe Implementation of Thrombolysis in Stroke registry between 2003 and 2011. Methods— We extracted from the Safe Implementation of Thrombolysis in Stroke registry (n=45 079) year of treatment, center code, DNT, sex, age, National Institutes of Health Stroke Scale, and comorbidity. For each center, the year they joined the registry and the annual volume of patients were determined ( Results— DNT was not available for 720 (1.6%) patients. The overall mean (SD) DNT was 73 (37) minutes with a median (interquartile range) of 67 (47–91) minutes. The DNT was 65 (46–90), 68 (50–92), and 72 (51–98) minutes for centers joined early (2003–2005), later (2006–2009), and recently (2009–2011), respectively. Center volume had more robust effect on DNT than year of treatment, and the shortest DNTs were seen in centers with volumes ≥100 patients/y. Earlier enrollment period was also associated with shorter delays. Conclusions— Centers that joined the registry earlier and those with high annual volume achieved shorter DNT than centers that joined later and low-volume centers. However, in most of the centers, DNT did not change much during the registry period. A multicenter project aiming to reduce DNT is warranted.