Objective: (i) To compare the prevalence and severity of depressive symptoms between men and women enrolled in a large heart failure (HF) registry. (ii) To determine gender differences in predictors of depressive symptoms from demographic, behavioral, clinical, and psychosocial factors in HF patients. Methods: In 622 HF patients (70% male, 61 ± 13 years, 59% NYHA class III/IV), depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9). Potential correlates were age, ethnicity, education, marital and financial status, smoking, exercise, body mass index (BMI), HF etiology, NYHA class, comorbidities, functional capacity, anxiety, and perceived control. To identify gender-specific correlates of depressive symptoms, separate logistic regression models were built by gender. Results: Correlates of depressive symptoms in men were financial status (p = 0.027), NYHA (p = 0.001); functional capacity (p < 0.001); health perception (p = 0.043); perceived control (p = 0.002) and anxiety (p < 0.001). Correlates of depressive symptoms in women were BMI (p = 0.003); perceived control (p = 0.013) and anxiety (p < 0.001). Conclusions: In HF patients, lowering depressive symptoms may require gender-specific interventions focusing on weight management in women and improving perceived functional capacity in men. Both men and women with HF may benefit from anxiety reduction and increased control.