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Objectives: Brain-derived neurotrophic factor (BDNF) as a biomarker of depressive symptoms manifests a novel role in the cardiovascular system. This study aims to indicate the association of BDNF levels between depressive symptoms and the cardiovascular prognosis in coronary heart disease (CHD) patients. Methods: Participants were recruited from hospitalized CHD patients between November 18, 2020 and November 26, 2021, in the First Affiliated Hospital of Shantou University Medical College. Serum BDNF levels were measured by the enzyme-linked immunosorbent assays. Depressive symptom was evaluated using Patient Health Questionnaire (PHQ-9). The cardiovascular events were the endpoint outcomes across the 12-month follow-up. Kaplan–Meier curves and Cox proportional hazards regression models were used to investigate the relationship of serum BDNF levels between depressive symptom and prognosis. Results: A total of 102 CHD patients (60.6 ± 10.4 year, 76% male) were enrolled. Based on the median serum BDNF levels, the participants were grouped into those “low BDNF (≤0.65 ng/mL)” versus “high BDNF (≥0.65 ng/mL).” CHD patients with low BDNF levels had a higher prevalence of depressive symptoms (PHQ–9 ≥10) compared with high BDNF levels. Within a median 540 days of follow-up, low serum BDNF increased the risk of cardiovascular events (adjusted hazard ratio = 3.26; 95% confidence interval = 1.18–9.02, P = 0.02) after adjustment for confounding factors. Conclusions: CHD patients with low serum BDNF levels were significantly associated with an increased risk of cardiovascular events, independently of depressive symptoms.