BACKGROUND: The red blood cell distribution width-to-albumin ratio (RAR) serves as an indicator of systemic inflammation and nutritional status. This study examines the relationship between RAR and depressive disorder in U.S. adults, utilizing data from the National Health and Nutrition Examination Survey (NHANES). METHODS: We applied logistic regression to evaluate the link between RAR and depressive risk, with its corresponding odds ratios (OR) and 95 % confidence intervals (CI) calculated. Restricted cubic spline (RCS) was adopted to assess the potential linear association, while the receiver operating characteristic (ROC) curve was used to evaluate the ability of RAR to predict the depressive risk, with the result presented as an area under the curve (AUC). RESULTS: After adjusting for relevant covariates, a positive association between RAR and clinically relevant depression persisted (OR = 1.33, 95 % CI: 1.18-1.51, P <
0.001). Participants in the highest RAR quartile exhibited a greater risk of clinically relevant depression than those in the lowest quartile (OR = 1.36, 95 % CI: 1.10-1.67, P = 0.005). A linear relationship between RAR and clinically relevant depression was identified (P for non-linear = 0.473), with RAR showing a strong predictive ability for depressive risk (AUC = 0.7467). Stratified analysis showed significant interactions among smoking (P = 0.045), marital status (P <
0.001), and RAR's effect on depression outcome. CONCLUSIONS: Elevated RAR is independently linked to clinically relevant depression, indicating its potential as a novel biomarker for mental health risk assessment. Further longitudinal studies are necessary to establish causality and evaluate its clinical relevance.