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Background and Aims: Previous observational data indicate that young adults treated with intravenous thrombolysis (IVT) for acute ischemic stroke have more favorable outcomes and less complications when compared to older adults. Given the limited data on this topic, we aimed to provide more evidence on clinical outcomes and safety in such patients, using a large international thrombolysis registry., Methods: In this prospective multicenter study, we used data from the Thrombolysis in Ischemic Stroke Patients (TRISP) registry from 1998 to 2020. Patients who received endovascular treatment (EVT), as only treatment or in addition to IVT, were not included in this cohort. Using multivariable regression models, we compared thrombolysed young patients aged 18-49 years with those aged ⩾50 years with regards to the following outcomes: favorable outcome in stroke survivors (modified Rankin Scale ⩽2), symptomatic intracranial hemorrhage (sICH) according to European Cooperative Acute Stroke Study II (ECASS II) criteria, and three-months all-cause death., Results: Of the 16,651 IVT treated patients, 1346 (8.1%) were 18-49 years. Young adults in TRISP were more often male (59.6% vs 54.0%), had a lower median NIHSS score on admission, 7 (4-13) versus 8 (5-15), and had less cardiovascular risk factors except for smoking (42.0% vs 19.0%) when compared to older patients. When compared to thrombolysed patients aged ⩾50 years, a favorable functional outcome was more likely in young adults: 81.9% versus 56.4%, aOR 2.30 (1.80-2.95), whilst sICH 1.6% versus 4.6%, aOR 0.45 (0.23-0.90) and death 2.3% versus 14.2%, aOR 0.21 (0.11-0.39) were less likely., Conclusions: Intravenous thrombolysis in young adults is independently associated with higher rates of favorable outcomes and lower rates of complications., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Nicolas Martinez-Majander reports funding from the Finnish Medical Foundation.Jukka Putaala reports personal fees from Bayer, Boehringer-Ingelheim, BMS-Pfizer, Abbott; Advisory board: Portola, Novo Nordisk, and Herantis Pharma, outside the submitted work.Yannick Béjot reports personal fees from BMS, Pfizer, Medtronic, Amgen, Boehringer-Ingelheim, Servier, NovoNordisk, Novartis, outside the submitted work.Peter Ringleb received speaker and advisory board honoraria from Boehringer Ingelheim, Bayer, BMS and Pfizer paid to the institution.Christoph Gumbinger received Research support from the Gesellschaft für Internationale Zusammenarbeit (GIZ), European Stroke Research Foundation (paid to the institution) and Study compensation from AstraZeneca/Alexion/ (paid to the institution); all outside the submitted work.Matthias Ungerer has received research support from the European Stroke Research Foundation (paid to the institution), outside the submitted work.Marialuisa Zedde reports personal fees from Amicus, Sanofi Genzyme, Takeda, outside the submitted work.Christian H Nolte reports personal fees from AstraZeneca/Abbot, Alexion,/ (paid to the institution);, Astra-Zeneca, Bristol-Myers Squibb, Daiichi Sankyo, Novartis, Pfizer, Portola and Takeda, all outside the submitted work.Ronen R Leker reports personal fees from IschemaView, Filterlex, Bayer, Biogen, Boeringer-Ingelheim, Abott, all outside of the submitted work.Visnja Padjen reports travel or speaker honoraria from Boehringer Ingelheim; honoraria from scientific advisory board from Medtronic, outside the submitted work.Andrea Zini reports speaker honoraria from CSL Behring, Alexion-Astra Zeneca and Daiichi Sankyo and advisory board honoraria from Bayer, Astra Zeneca, all outside of the submitted work.Susanne Wegener reports speaker honoraria from Amgen, Springer, Teva Pharma, ADVISIS-AG, FOMF, Astra Zeneca, and a consultancy fee from Bayer and Novartis; all outside this work.Miriam Heldner reports grants from SITEM Research Support Funds and Swiss National Science Foundation, Swiss Heart Foundation, not directly related to this manuscript.Ivana Berisavac reports speaker honoraria from Medtronic.George Ntaios reports advisory boards/research support/speaker fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Javelin Medical, Novartis, and Sanofi; Clinical trial steering/executive committees for Janssen and Javelin Medical. All paid directly to the University of Thessaly. All outside of the submitted work.The other authors report nothing to disclose.