Introduction: Previous studies have shown biases in screening for toxicologic substances among stroke patients but have limited generalizability. Our objective was to investigate predictors of the use of drug screens among stroke patients in a large population based study. Methods: The Greater Cincinnati Northern Kentucky Stroke Study is a population-based study of stroke cases ascertained from a biracial population of 1.3 million people in a 5-county region of southern Ohio/northern Kentucky. All hospital ascertained cases of stroke (ischemic (IS), transient ischemic attack (TIA), hemorrhagic (ICH), subarachnoid hemorrhage (SAH)), occurring during calendar year 2015 were included. Trained study nurses abstracted data on whether a drug screen was ordered (between emergency department (ED) presentation and hospital discharge). Screening tests for alcohol were not included. Multivariable logistic regression was used to identify predictors of use of a drug screen. Potential predictors were patient sex, age, race, select comorbidities, smoking status, stroke severity (NIHSS), treatment location and stroke type. Results: Of 3865 stroke cases (53.8% women, 20.8% black, mean age 69.7(14.8) years), 12.0% had a drug screen performed. Adjusted, black race (aOR 1.93 95%CI 1.52-2.44), current smoking (aOR 1.97 95%CI 1.58-2.47), higher NIHSS (aOR 1.22 95%CI 1.15-1.28 per 5 unit increase) and being treated in an academic ED (aOR 2.04, 95%CI 1.62-2.55) increased the likelihood of a drug screen, while female gender (aOR 0.75 95%CI 0.60-0.93) and older age (aOR 0.61 per 10 years, 95%CI 0.56-0.66) decreased the likelihood. Conclusions: In a large population based study of stroke patients, drug screens were more likely to be ordered in men, blacks, smokers, younger patients, and those seen in academic EDs. It is unknown whether these trends are similar among hospitalized patients with other diagnoses. Additionally, current evidence suggests that such differential testing may lead to missed counselling opportunities in those not tested as well as lower likelihood of thrombolytic treatment in those who are tested. Future research should investigate the yield of such drug screens and explore whether guidelines in ordering drug tests could help to avoid testing biases.