Purpose: The primary aim was to determine whether a shock index (SI) ≥ 1 in adult trauma patients was associated with increased in-hospital mortality compared to an SI < 1. Methods: This systematic review including a meta-analysis was performed in accordance with the PRISMA guidelines. EMBASE, MEDLINE, and Cochrane Library were searched, and two authors independently screened articles, performed the data extraction, and assessed risk of bias. Studies were included if they reported in-hospital, 30-day, or 48-h mortality, length of stay, massive blood transfusion or ICU admission in trauma patients with SI recorded at arrival in the emergency department or trauma center. Risk of bias was assessed using the Newcastle–Ottawa Scale, and the strength and quality of the body of evidence according to GRADE. Data were pooled using a random effects model. Inter-rater reliability was assessed with Cohen’s kappa. Results: We screened 1350 citations with an inter-rater reliability of 0.90. Thirty-eight cohort studies were included of which 14 reported the primary outcome. All studies reported a significant higher in-hospital mortality in adult trauma patients with an SI ≥ 1 compared to those having an SI < 1. Twelve studies involving a total of 348,687 participants were included in the meta-analysis. The pooled risk ratio (RR) of in-hospital mortality was 4.15 (95% CI 2.96–5.83). The overall quality of evidence was low. Conclusions: This systematic review found a fourfold increased risk of in-hospital mortality in adult trauma patients with an initial SI ≥ 1 in the emergency department or trauma center.