BACKGROUND Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can manifest after a traumatic event where the individual perceives a threat to his or her life or that of others. Its estimated prevalence in the European population is 0.7% to 1.9%. According to the “dose-response” model, individuals who are most exposed to traumatic events are most at risk of developing PTSD. Hence, it is unsurprising that studies have observed a higher prevalence among the military population, ranging from 10% to 18%, or even up to 45%. This project’s overall goal is to evaluate the primary prevention actions that can strengthen the resilience of at-risk professionals, notably military personnel, in the short term, with the medium- to long-term aim of preventing the occurrence of PTSD and improving the patient’s prognosis. OBJECTIVE This study’s objectives are (1) to design a primary prevention program for PTSD, tailored to the studied military population and compatible with operational constraints; and (2) to implement and validate the Primary Prevention of Posttraumatic Stress Disorder in Military Professionals (PREPARE) program in the short term with operational personnel belonging to the French Mountain Infantry Brigade. METHODS This is a single-center, prospective, randomized, parallel-group controlled cohort study. The cohort is divided into 2 groups: the nonintervention group receives no training, and the intervention group follows a dedicated prevention program (structured into 8 workshops and 2 debriefing and practice reinforcement workshops). Each participant is evaluated 4 times (at inclusion, +4 months, +6 months, and +12 months). During each visit, participants complete several psychosocial questionnaires (which take 15-80 minutes to complete). Samples (a 30-mL blood sample and three 5-mL saliva samples) are collected on 3 occasions: at inclusion, +4 months, and +12 months. Emotional reactivity (electrocardiogram and electrodermal activity) is measured before, during, and after the classic and the emotional Stroop task. RESULTS The project is currently ongoing, and results are expected to be published by the end of 2024. CONCLUSIONS The study adopts an integrative approach to the processes that play a role in the risk of developing PTSD. Our biopsychosocial perspective makes it possible to target levers related to factors specific to the individual and socio-professional factors. The following dimensions are addressed: (1) biophysiology (by studying markers of the neurobiological stress response, wear and tear, and vulnerability phenomena and reinforcing the flexibility of the autonomic nervous system), (2) psychology (by facilitating and measuring the development of flexible coping strategies to deal with stress and evaluating the moderating role of the individual’s sense of duty in the development of PTSD), and (3) social (by facilitating community strategies aimed at reducing stigmatization and supporting the use of care by professionals in difficulty, in the institutional context). CLINICALTRIAL ClinicalTrials.gov NCT05094531; https://clinicaltrials.gov/study/NCT05094531 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/47175