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Background Cardiovascular disease (CVD) is the leading cause of mortality worldwide, while depression is highly prevalent in this patient population and has long been regarded as an independent risk factor for increased mortality. However, recent evidence suggests that this association may be influenced by symptom overlap and residual confounding that has not been fully accounted for.Objectives This study aimed to evaluate the association between clinically significant depressive symptoms and the risk of all-cause, cardiovascular and non-cardiovascular mortality in adults with CVD.Methods We conducted a secondary analysis of 2064 adults with a history of CVD using data from the National Health and Nutrition Examination Survey 2011–2018 linked with the National Death Index. Depression was defined using the Patient Health Questionnaire-9 with a cut-off score of 10 or higher. Primary outcomes were all-cause, cardiovascular and non-cardiovascular mortality. Statistical analyses were performed using R software. We employed multivariable Cox regression models as well as propensity score matching and inverse probability weighting to control for potential confounders.Results Over a median follow-up of 4.67 years, 403 deaths were recorded. In an adjusted multivariable Cox model controlling for age, sex and race, depression was associated with an increased risk of all-cause mortality (HR 1.33; 95% CI 1.02 to 1.75) and non-cardiovascular mortality (HR 1.46; 95% CI 1.04 to 2.05). However, after applying propensity score matching and inverse probability weighting, these associations were no longer statistically significant for any mortality outcome.Conclusions After rigorous adjustment for confounders and comorbidities, depression was no longer identified as an independent risk factor for mortality among patients with CVD.