BackgroundThis study investigated the longitudinal associations between serum BDNF (sBDNF) levels measured early after injury and the onset of post-traumatic stress disorder (PTSD) across two years. MethodsPatients with moderate to severe physical injuries were enrolled from a trauma center. At baseline, sBDNF levels were measured and a comprehensive socio-demographic and clinical data were collected. The range of time from physical injuries to blood collection was 1–28 days, with a median (IQR) of 8.0 (6.0) days. PTSD diagnoses were determined at 3, 6, 12, and 24 months post-injury using the CAPS-5. Linear regression analyses assessed the relationship between sBDNF levels and PTSD diagnoses. ResultsOut of 923 patients, 112 (12.1 %) developed PTSD during the study. Prevalence rates were 8.8 % at 3 months, 7.6 % at 6 months, 4.8 % at 12 months, and 3.7 % at 24 months. Significantly, lower sBDNF levels were associated with PTSD at 12 and 24 months, after adjusting for covariates and applying Bonferroni corrections, but not at earlier assessments. LimitationsFocusing on patients with moderate to severe injuries from a single center may limit the findings' generalizability. ConclusionEarly post-injury sBDNF levels are predictive biomarkers for PTSD, especially significant at 12 and 24 months post-injury.