Background: Perceived control has been suggested as a modifiable factor associated with health-related quality of life (HRQOL). However, the relationship between perceived control and HRQOL has not been evaluated in patients with heart failure (HF). The purpose of this study was to determine whether perceived control independently predicts HRQOL in HF patients. Methods: A total of 423 HF patients were included. Hierarchical linear regression was performed to determine the independent association of perceived control to HRQOL after controlling for covariates. Results: Higher levels of perceived control were associated with better HRQOL in univariate analysis. However, this relationship was strongly attenuated after controlling for relevant demographic, clinical, and psychological factors; the variance in HRQOL explained by the addition of perceived control to this model was small (1.4%). Conclusions: We found only a weak relationship between perceived control and HRQOL when considered in the presence of demographic, clinical, and psychological factors.