Introduction: Peri-procedural acute ischemic stroke (AIS) risk after Transcatheter Aortic Valve Replacement (TAVR) is between 3% to 6.7%, and administration of IV-tPA for its management is not well studied. We analyzed patients who had peri-procedural AIS after TAVR and compared those treated with IV-tPA to those who were not. Methods: Data were retrospectively abstracted for patients with an AIS after TAVR within a large regional healthcare system. Baseline demographics were analyzed using the Pearson Chi-Square test. Post AIS outcomes (bleeding events, cardiac events, and functional outcomes) were analyzed using the Pearson Chi Square test and Kruskal-Wallis test. Results: From 2011 - 2019, 779 patients underwent TAVR, of which 22 (2.6%) had peri- procedural AIS. 8 received tPA and 14 did not. There was no difference in baseline characteristics. See Table 1. During index hospitalization, there were more groin bleeding events in the tPA group (6 {75%} in tPA vs. 0 {0%} in non-tPA p=0.005). More patients in the tPA group had a trend towards a drop in hemoglobin by 2 g/dL and total aggregate bleeding events. There were no differences in symptomatic ICH, other intracranial bleeding, post-procedural Afib/flutter, post-procedural new CHF, and discharge functional outcomes. At 90 days, there were no differences in safety outcomes and median 90-day mRS. Conclusions: This is the largest case series to describe patients who had AIS after TAVR and received tPA. There was no difference between adverse neurological or cardiac outcomes at discharge and 90 days in the tPA group vs. non-tPA group. More tPA patients had groin bleeding, which did not cause any long-term functional impairment. There was a trend toward tPA patients having a lower discharge NIHSS. Overall, tPA appears to be a safe intervention for AIS after TAVR. More evidence is needed to determine its efficacy in TAVR patients.