Studies that have analyzed the association between cannabis use and acute ischemic stroke (AIS) have provided conflicting results. In this study, we aim to determine the association of recent cannabis use detected through urine drug screen (UDS) among patients admitted with AIS. A retrospective observational study was performed using the medical records database. All patients aged 18 years and older admitted from January 1, 2015, to December 31, 2017, who underwent urine toxicology testing on admission were included in the analysis. Multivariate logistic regression analysis was performed to analyze independent association between recent cannabis use and AIS. A total of 9,350 patients were determined to have undergone UDS during admission, and 18% (1,643) of this had a positive urine cannabis test. Unadjusted risk ratio showed a 50% decrease in risk of AIS among cannabis users (risk ratio = 0.505, 95% confidence interval [CI] 0.425-0.600). The effect was lost after adjusting for age, race, ethnicity, sickle cell disease, dyslipidemia, hypertension, obesity, diabetes mellitus, cigarette smoking, atrial fibrillation, and other cardiac conditions (odds ratio 1.038, 95% CI 0.773-1.394). This is one of the few studies analyzing the association of recent cannabis use and AIS using admission urine toxicology test independent of polysubstance use. Although our study has limitations, we did not find an independent association between recent cannabis use and the incidence of AIS. Further studies using urine toxicology tests with larger sample size and including dosage of cannabis exposure should be conducted.