Background: The 6th International Consensus Statement on Concussion in Sport guidelines identified that measuring autonomic nervous system dysfunction using orthostatic vital signs (VSs) is an important part of the clinical evaluation; however, there are limited data on the frequency of autonomic nervous system dysfunction captured via orthostatic VSs after concussion. Purpose: To compare orthostatic changes in heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) between athletes with acute sport-related concussion (SRC) and control athletes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We compared 133 athletes (mean age, 15.3 years; age range, 8-28 years; 45.9% female) with acute SRC (<30 days after injury) with 100 control athletes (mean age, 15.7 years; age range, 10-28 years; 54.0% female). Given the broad age range eligible for study inclusion, participants were subdivided into child (younger than 13 years of age), adolescent (13-17 years of age), and adult (18 years of age and older) age groups for subanalyses. Participants completed a single standard orthostatic VS evaluation including HR, SBP, and DBP in the supine position then immediately and 2 minutes after standing. Linear regression was used to compare delayed supine-to-standing changes in HR, SBP, and DBP as a continuous variable (ΔHR, ΔSPB, and ΔDBP) between groups, and logistic regression was used to compare patients with positive orthostatic VS changes (sustained HR increase ≥30 beats per minute [bpm], SBP decrease ≥20 mm Hg, and DBP ≥10 mm Hg at 2 minutes) between groups, accounting for age and sex. Results: Between-group differences were present for delayed ΔHR (18.4 ± 12.7 bpm in patients with SRC vs 13.2 ± 11.0 bpm in controls; P = .002) and ΔSPB (–3.1 ± 6.6 bpm in patients with SRC vs –0.4 ± 6.5 bpm in controls; P = .001), with positive orthostatic HR changes present more frequently in patients with SRC (18% vs 7%; odds ratio, 2.79; P = .027). In the SRC group, a weak inverse relationship was present between age and ΔHR ( r = –0.171; P = .049), with positive orthostatic HR findings occurring primarily in the child and adolescent SRC subgroups. Conclusion: Patients with acute SRC had greater orthostatic VS changes compared with controls, the most prominent being sustained HR elevations. Clinical evaluation of autonomic change after SRC via standard orthostatic VS assessment may be a helpful clinical biomarker in the assessment of SRC, especially in children and adolescents.