Psychological stress is a well-established risk factor for cardiovascular disease (CVD). Heart rate variability (HRV)-biofeedback could significantly reduce stress levels and improve autonomic nervous system function and cardiovascular endpoints. We aimed to systematically review the literature to investigate the impact of HRV modulation through HRV-biofeedback on clinical outcomes in patients with CVD. A literature search was performed in the following databases: MEDLINE (PubMed), Embase, and Cochrane from the inception until 1 October 2021. Patients in the HRV-biofeedback group had significantly lower rates of all-cause readmissions than patients who received psychological education (respectively, p = 0.028 and p = 0.001). Heart failure following HRV-biofeedback displayed an inverse association with stress and depression (respectively, p = 0.022 and p = 0.033). When stratified according to left ventricular ejection fraction (LVEF), patients with LVEF >/= 31% showed improved values of the 6 min walk test after HRV-biofeedback interventions (p = 0.05). A reduction in systolic and diastolic blood pressure associated with HRV-biofeedback was observed (p < 0.01) in pre-hypertensive patients. HRV-biofeedback had beneficial effects on different cardiovascular diseases documented in clinical trials, such as arterial hypertension, heart failure, and coronary artery disease. A standard breathing protocol should be applied in future studies to obtain equivalent results and outcomes. However, data regarding mortality in patients with coronary artery disease are scarce and need further research.