Introduction: Heart failure (HF) accounts for 30% of all global deaths and Asians are likely to suffer from HF 10 years earlier than their Western counterparts. Low self-efficacy and poor health-related quality of life (HRQoL) have been reported in patients with HF. Methodology: A descriptive correlational design was adopted to investigate the associations between self-efficacy and HRQoL in 91 patients with HF in Singapore. Results: Patients with HF demonstrated moderately good self-efficacy (M = 3.05, SD = 0.61) and HRQoL (M = 22.48, SD = 18.99). Significant differences were found between total self-efficacy scores and education levels (p = .05), and between overall HRQoL and smoking status (p < .05). Self-efficacy was not significantly correlated to HRQoL. Smoking status, HF classification, and self-efficacy in maintaining function predicted HRQoL. Discussion: Health care professionals should assess each patient’s demographics, smoking status, and clinical condition before delivering individualized education to enhance their self-efficacy and, in turn, overall HRQoL.