Importance: The extended Focused Assessment With Sonography for Trauma (E-FAST) has become a cornerstone of the diagnostic workup in patients with trauma. The added value of a diagnostic workup including an E-FAST to support decision-making remains unknown. Objective: To determine how often an immediate course of action adopted in the resuscitation room based on a diagnostic workup that included an E-FAST and before whole-body computed tomography scanning (WBCT) in patients with blunt trauma was appropriate. Design, Setting, and Participants: This cohort study was conducted at 6 French level I trauma centers between November 5, 2018, and November 5, 2019. Consecutive patients treated for blunt trauma were assessed at the participating centers. Data analysis took place in February 2022. Exposures: Diagnostic workup associating E-FAST (including abdominal, thoracic, pubic, and transcranial Doppler ultrasonography scan), systematic clinical examination, and chest and pelvic radiographs. Main Outcomes and Measures: The main outcome criterion was the appropriateness of the observed course of action (including abstention) in the resuscitation room according to evaluation by a masked expert panel. Results: Of 515 patients screened, 510 patients (99.0%) were included. Among the 510 patients included, 394 were men (77.3%), the median (IQR) age was 46 years (29-61 years), and the median (IQR) Injury Severity Score (ISS) was 24 (17-34). Based on the initial diagnostic workup, no immediate therapeutic action was deemed necessary in 233 cases (45.7%). Conversely, the following immediate therapeutic actions were initiated before WBCT: 6 emergency laparotomies (1.2%), 2 pelvic angioembolisations (0.4%), 52 pelvic binders (10.2%), 41 chest drains (8.0%) and 16 chest decompressions (3.1%), 60 osmotherapies (11.8%), and 6 thoracotomies (1.2%). To improve cerebral blood flow based on transcranial doppler recordings, norepinephrine was initiated in 108 cases (21.2%). In summary, the expert panel considered the course of action appropriate in 493 of 510 cases (96.7%; 95% CI, 94.7%-98.0%). Among the 17 cases (3.3%) with inappropriate course of action, 13 (76%) corresponded to a deviation from existing guidelines and 4 (24%) resulted from an erroneous interpretation of the E-FAST. Conclusions and Relevance: This prospective, multicenter cohort study found that a diagnostic resuscitation room workup for patients with blunt trauma that included E-FAST with clinical assessment and targeted chest and pelvic radiographs was associated with the determination of an appropriate course of action prior to WBCT.