Introduction: Prescription stimulants are an effective FDA approved treatment for attention deficit hyperactivity disorder (ADHD) however their safety has come under scrutiny. Multiple studies demonstrate safe use in pediatric populations, but prescriptions are increasing to adults and it is not evident which comorbidities might place people at risk of adverse outcomes. The aim of this study is to identify risk factors of adverse cardiovascular events for individuals exposed to stimulants across the lifespan. Methods: We conducted a case control study utilizing the TriNetX research network database. Individuals were included for study if they were younger than 90 years old and prescribed stimulants between January 1, 2010 and December 31, 2020. We utilized summary statistics, chi2, and multivariate logistic regression to identify risk factors for cardiovascular events. Results: Of the 987,762 individuals prescribed stimulants, 49,902 experienced an adverse cardiovascular event. Individuals with atherosclerotic heart disease had the highest odds of adverse events (aOR = 36.7, p < 0.001). Hypertension (aOR = 2.78 p < 0.001), cocaine use (aOR = 1.64 p < 0.001), and anxiety (aOR = 1.46 p < 0.001) were also strongly predictive of adverse outcomes, but risk varied by age. Conclusions: Atherosclerotic heart disease and its antecedents pose the greatest risk for cardiovascular events for people prescribed stimulants. Mental health diagnoses are also independent predictors and age may be an effect modifier of these relationships. ADHD was not an independent risk factor for major adverse cardiovascular events when controlling for other biopsychosocial variables in adult populations. Additional research focused on predictive models and prospective studies may be warranted to better inform clinical decisions regarding stimulant prescriptions for the broad demographic of patients that may benefit from these medications.