Background: With changes in state laws, cannabis is now more accessible in many parts of the United States. The drug has previously been associated with a higher incidence of acute ischemic stroke (AIS). Our study analyzed the effect of cannabis use on AIS outcomes., Methods: The 2019 National Inpatient Sample from Healthcare Cost and Utilization Project and Agency for Healthcare Research and Quality was used to evaluate the AIS patients ages 25 and more. Cannabis users were compared with nonusers. Their mortality risks were also assessed., Results: Five hundred thirty-nine thousand eight hundred eighty patients with AIS were in our study and 8850 used cannabis. Among the cannabis users with AIS, 69.8% were males, 50.6% were white, 61.8% were aged 46 to 65, 32.1% used Medicaid, 86.1% were nonobese, 72.0% were nondiabetics, 81.7% had hypertension, 80.7% did not have a history of alcohol abuse, and 77.5% were smokers (nicotine). Only 12.8% of cannabis users reported any cardiac dysrhythmia, whereas 5.4% required mechanical thrombectomy, and 8.0% received intravenous tissue plasminogen activator (tPA).After adjusting the variables, cannabis users covered by Medicare, with diabetes, a history of alcohol abuse, cardiac dysrhythmias, and who underwent mechanical thrombectomy had a higher risk of dying. The overall adjusted odds ratio of dying among cannabis users with AIS was 0.603 (95% CI, 0.504-0.722, P <0.01)., Conclusions: Although the overall mortality risk seems to be lower among cannabis users, those with certain risk factors still present higher mortality risks. Patients with cannabis use should therefore be monitored closely for possible complications and mortality after AIS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)