Heart failure (HF) is a chronic condition requiring continuous self-care. Health literacy is increasingly recognized as a key factor of self-care behaviors in patients with chronic diseases. Recently, frailty in chronic diseases has also been associated with self-care behaviors. However, relationships among health literacy, frailty, and self-care in the HF population are not well understood. Therefore, this cross-sectional study aimed to identify the impact of health literacy and frailty on self-care behaviors in patients with HF. Data were collected from 281 adults attending a cardiovascular outpatient clinic in Korea. Health literacy, frailty, and self-care behaviors were measured using Korean-validated instruments. The mean scores of health literacy and self-care behaviors were 8.89 (+/-3.44) and 31.49 (+/-5.38), respectively. The prevalence of frailty was around 26.3%. Health literacy was significantly associated with frailty and self-care behaviors. In a hierarchical linear regression analysis, health literacy was a significant determinant of self-care behaviors after adjusting for confounding variables, but frailty was not. Educational level was also a significant predictor of self-care behaviors. Our main findings showed that health literacy can facilitate improvements in HF self-care behaviors. Healthcare professionals should assess patients' health literacy and educational backgrounds when designing self-management programs.