Objective: Although stroke guidelines recommend antiplatelets be started 24 hoursafter tissue plasminogen activator (tPA), select mechanical thrombectomy (MT)patients with luminal irregularities or underlying intracranial atherosclerotic diseasemay benefit from earlier antiplatelet administration. Methods: We explore the safety of early (< 24 hours) post-tPA antiplatelet use byretrospectively reviewing patients who underwent MT and stent placement for acuteischemic stroke from June 2015 to April 2018 at our institution. Results: Six patients met inclusion criteria. Median presenting and pre-operativeNational Institutes of Health Stroke Scale scores were 14 (Interquartile Range [IQR]5.5-17.3) and 16 (IQR 13.7-18.7), respectively. Five patients received standard intravenous(IV) tPA and one patient received intra-arterial tPA. Median time from symptomonset to IV tPA was 120 min (IQR 78-204 min). Median time between tPA and antiplateletadministration was 4.9 hours (IQR 3.0-6.7 hours). Clots were successfullyremoved from the internal carotid artery (ICA) or middle cerebral artery (MCA) in 5patients, the anterior cerebral artery (ACA) in one patient, and the vertebrobasilarjunction in one patient. All patients underwent MT before stenting and achievedthrombolysis in cerebral infarction 2B recanalization. Stents were placed in the ICA(n=4), common carotid artery (n=1), and basilar artery (n=1). The median time fromstroke onset to endovascular access was 185 min (IQR 136-417 min). No patientsexperienced symptomatic post-procedure intracranial hemorrhage (ICH). Medianmodified Rankin Scale score on discharge was 3.5. Conclusions Antiplatelets within 24 hours of tPA did not result in symptomatic ICHin this series. The safety and efficacy of early antiplatelet administration after tPA inselect patients following mechanical thrombectomy warrants further study.