BACKGROUND Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition, epidemiology, and change in incidence over time are poorly understood. We aimed to describe the incidence of MOF in the context of different MOF definitions, study inclusion criteria, and its change over time. METHODS Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for articles published between 1977 and 2022 in English and German. Random-effects meta-analysis was performed when applicable. RESULTS The search returned 11,440 results, of which 842 full-text articles were screened. Multiple organ failure incidence was reported in 284 studies that used 11 unique inclusion criteria and 40 MOF definitions. One hundred six studies published from 1992 to 2022 were included. Weighted MOF incidence by publication year fluctuated from 11% to 56% without significant decrease over time. Multiple organ failure was defined using four scoring systems (Denver, Goris, Marshall, Sequential Organ Failure Assessment [SOFA]) and 10 different cutoff values. Overall, 351,942 trauma patients were included, of whom 82,971 (24%) developed MOF. The weighted incidences of MOF from meta-analysis of 30 eligible studies were as follows: 14.7% (95% confidence interval [CI], 12.1–17.2%) in Denver score >3, 12.7% (95% CI, 9.3–16.1%) in Denver score >3 with blunt injuries only, 28.6% (95% CI, 12–45.1%) in Denver score >8, 25.6% (95% CI, 10.4–40.7%) in Goris score >4, 29.9% (95% CI, 14.9–45%) in Marshall score >5, 20.3% (95% CI, 9.4–31.2%) in Marshall score >5 with blunt injuries only, 38.6% (95% CI, 33–44.3%) in SOFA score >3, 55.1% (95% CI, 49.7–60.5%) in SOFA score >3 with blunt injuries only, and 34.8% (95% CI, 28.7–40.8%) in SOFA score >5. CONCLUSION The incidence of postinjury MOF varies largely because of lack of a consensus definition and study population. Until an international consensus is reached, further research will be hindered. LEVEL OF EVIDENCE Systematic Review and Meta-analysis; Level III.