Background: First responders are at risk for developing symptoms of post-traumatic stress disorder (PTSD). Especially, body recovery duties and nuclear disaster response were known as challenging missions that can induce severe adverse psychological responses for a long time. The 2011 Great East Japan Earthquake (GEJE), an unprecedented complex disaster (i.e., earthquake/tsunami/nuclear accident), provided us with a unique opportunity to explore these risk factors and their relative influence for PTSD. Methods: Of approximately 70 000 eligible Japan Ground Self-Defense Force (JGSDF) first responders, 56 388 enrolled in this 6-year prospective cohort study. The data were collected at eight time points: one, six, 12, 24, 36, 48, 60, and 72 months post-mission completion. The Impact of Event Scale–Revised assessed PTSD symptoms; scores of ≥25 were defined as probable PTSD. Professional disaster experience (i.e., duties with body recovery or radiation exposure risk), sociodemographic factors (e.g., disaster–victim status) and working conditions (e.g., deployment length) were investigated. Cox proportional hazard models assessed the risk factors for incidences of probable PTSD. Findings: The cumulative incidence of probable PTSD was 6·75%. The classes categorized by baseline severity of PTSD symptoms demonstrated a high degree of rank-order stability over time. Rather than professional disaster experience, sociodemographic factors and working conditions showed strong independent association with the incidence of probable PTSD: disaster-victim status (hazard ratio [HR]=1·96; 95% CI 1·72-2·24), deployment length of ≥3 months (vs. <1 month; HR=1·75; 95% CI 1·52-2·03), older age (≥46 vs. ≤25 years; HR=2·28; 95% CI 1·79-2·91), and post-deployment overwork of ≥3 months (vs. little to none; HR=1·61; 95% CI 1·39-1·87). Interpretation: In the future, first responders’ PTSD symptoms might be mitigated by shortening deployment length, avoiding post-deployment overwork, and paying special attention to personnel with disaster-victim status or older age. Efforts to alleviate responders’ initial symptoms will be required. Funding Statement: This study was supported by the Japanese Society for the Promotion of Science KAKENHI Grant Number: 26461779. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Approval to perform this research was obtained from the Ethics Committee of the National Defense Medical College (Approval No. 2108). All data were anonymized before the statistical analyses.