ABSTRACT Inflammatory processes may contribute to running‐related injury (RRI) susceptibility, yet the predictive value of baseline inflammatory biomarkers remains unclear. This prospective study investigated whether baseline biochemical markers of inflammation predict RRI occurrence in healthy individuals over 1 year, while accounting for training, physiological, and injury history variables. A total of 1315 healthy individuals (recreational runners and inactive controls) were followed for 12 months with prospective injury surveillance. Baseline blood samples were analyzed for inflammatory markers. Multivariable logistic regression examined associations between baseline biomarkers and RRI occurrence, adjusting for age, sex, peak oxygen consumption, weekly running distance, total body fat, and history of musculoskeletal trauma. Significant predictors of RRI included baseline tumor necrosis factor alpha (TNF‐α) (OR per 1 pg/mL: 1.25, 95% CI: 1.08–1.44), history of musculoskeletal trauma (OR: 1.42, 95% CI: 1.06–1.90), weekly running distance, and age. Interleukin‐1 receptor antagonist (IL‐1RA) showed a modest protective association (OR per 10 pg/mL: 0.99, 95% CI: 0.99–1.00). However, the model demonstrated limited discriminatory ability (AUC = 0.66), indicating that baseline inflammatory markers alone are insufficient for individual‐level injury prediction. Baseline TNF‐α and IL‐RA are significantly associated with RRI occurrence, suggesting that inflammatory phenotype contributes to injury susceptibility. However, TNF‐α and IL‐1RA cannot serve as reliable standalone screening tools, and our findings indicate that baseline inflammatory phenotype represents one component of multifactorial injury risk. While baseline TNF‐α and IL‐1RA measurements are unlikely to transform clinical practice in isolation, understanding inflammatory contributions to injury susceptibility may inform more effective injury‐prevention strategies.