CONTEXT: An estimated 15.3 million adolescent students are enrolled in U.S. high schools, with approximately 7.8 million participating in athletics. Researchers have examined various demographics in high school athletes; however, athletic participation may play a larger role in test performance than previously thought. Currently, investigations of concussion assessment may rely on uninjured athletes as controls. However, due to the intense nature of athletics, this may not be an appropriate practice. OBJECTIVE: To examine differences between athletes and nonathletes using a common computerized neuropsychological test. DESIGN: Retrospective cross-sectional study. SETTING: High schools from a school district in Columbus, OH. PATIENTS OR OTHER PARTICIPANTS: A total of 662 adolescent high school students (athletes: n = 383, female n = 18; nonathletes: n = 279, female n = 193). MAIN OUTCOME MEASURE(S): Participants were administered a computerized neuropsychological test battery (Immediate Post-Concussion Assessment and Cognitive Test[ImPACT]) during baseline concussion assessment. Differences between groups were established for output composite scores. RESULTS: Differences were found between athletes and nonathletes in composite reaction time ( F1,522 = 14.855, P < .001) and total symptom score ( F1,427 = 33.770, P < .001). Nonathletes reported more symptoms, whereas athletes had faster reaction times. No differences were present in composite verbal memory, composite visual memory, composite visual motor, or composite impulse control ( P > .05). CONCLUSIONS: Symptom reporting and reaction time differed between high school athletes and nonathletes. Participation in extracurricular activities may lead to cognitive differences in adolescents that can influence performance on the Immediate Post-Concussion Assessment and Cognitive Test battery. Researchers should account for these differences in baseline performance when making concussion diagnostic and management decisions.