Background: Stimulant use disorder is a worldwide problem. Users present to the ED for diverse reasons including trauma, chest and abdominal pain, altered mental status, stroke, suicidality, and skin infection. Objective: To determine what differences exist between stimulant users. Methods: We compared Stimulant users presenting to an urban ED Level I trauma center over a 3-month period with toxicology screens positive for cocaine and/or methamphetamine. Results: Of 718 subjects (465 male, 253 female), 610 (85%) were positive for methamphetamine, 80 (11%) cocaine, and 28 (4%) both. Significant racial differences existed, but not for age, gender, and insurance status. Ethanol co-ingestion was higher for cocaine users, otherwise no significant differences were detected for laboratory values and maximum heart rate, and systolic/diastolic blood pressure. For presenting complaint, the proportion of cocaine users was higher for trauma and lower for altered level of consciousness than other subgroups. There was no significant difference in proportion of subjects admitted to the hospital, but cocaine users had a higher rate of elopement and were placed on 72-h psychiatric holds and/or transferred to inpatient psychiatric facilities at a significantly lower rate than the other subgroups. Conclusion: Cocaine users were more likely to present with trauma, elope from the ED, and have alcohol intoxication. Methamphetamine users were more likely to be Caucasian, have altered level of consciousness, be placed on psychiatric holds, or transferred to inpatient psychiatric facilities. These differences may be explained by regional preferences, socialization, personality types, and the unique neuropsychopharmacological differences between cocaine and methamphetamine.