To assess the level of self-efficacy in patients with heart failure (HF), and identify differences between important subgroups including sex, and to identify the determinants of high self-efficacy. This was a pooled cross-sectional analysis of 2,030 patients from four prospective studies conducted within the German Competence Network Heart Failure. We used the Self-efficacy Subscale and the Overall Summary Score (OSS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) to assess self-efficacy and health-related quality of life. The cut-off of 75 score points was used for the dichotomization into high (≥75) vs low (<75) self-efficacy. Depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9). A total of 1,615 patients with HF provided complete self-efficacy scores: mean age 66.6±12.3 years, 431 (27%) women. Mean self-efficacy was 67.5±24.9, with 907 patients (56.2%) showing high self-efficacy and 708 patients (43.8%) showing low self-efficacy. Men had higher self-efficacy scores than women (68.7±24.5 vs. 64.2±26.0; p=0.001). Multivariable logistic regression identified KCCQ-OSS (OR per 5-point increase 1.08, 95%CI 1.04-1.12), female sex (OR 0.72, 95%CI 0.56-0.94), depressive symptoms (OR per 3-point increase in PHQ-9 0.90, 95%CI 0.83-0.98), and acute HF (0.46, 95% CI 0.34-0.62) as important predictors of high self-efficacy. In patients with HF, women seemed to exhibit lower self-efficacy than men. Health-related quality of life and psychological well-being were dominant determinants of self-efficacy. Future studies should investigate the role of self-efficacy as a therapeutic target for tailored and sex-specific nursing interventions.