Objective: People with multiple prior concussions might be at risk for greater acute effects from a future concussion. We examined cognitive test performance acutely after a concussion among adolescent athletes who reported a history of two or more concussions. Method: A total of 39,161 adolescent athletes underwent baseline testing and 3,730 were re-assessed following a suspected concussion. Of those with a suspected injury, 467 without co-occurring neurodevelopmental problems were evaluated within 3 days of injury and 37 reported two or more prior concussions (i.e., the index injury represents at least their third concussion). Using a nested case-control design, each participant with two or more prior concussions was individually matched to two youth without a history of concussions (“injured controls”; index injury represents their first concussion) based on age, sex, and sport (total n = 111; age: M = 16.2, SD = 1.1). ImPACT® composite scores were examined with a Multivariate Mixed ANOVA (Between-Subjects = group, Within-subjects = time). Results: There was a main effect of time (Λ = 0.86, F = 4.21, p < 0.01, ηp2 = 0.14), with worse cognitive test performance acutely following injury, specifically in Verbal Memory (p < 0.001, ηp2 = .11, medium effect) and Reaction Time (p = .02, ηp2 = .05, small effect). There was not a significant main effect for group (Λ = 0.94, F = 1.72, p = 0.15) or group-by-time interaction (Λ = 0.95, F = 1.29, p = 0.28). Conclusions: Both groups had worse verbal memory and reaction time acutely following concussion, but the groups had similar magnitudes of decline from baseline. Having a history of two or more prior concussions was not associated with worse cognitive test performance acutely following a subsequent concussion.