Background: Many patients with heart failure (HF) experience persistent symptoms and poor health-related quality of life (HRQOL). Psychosocial distress is common and adversely affects HF symptoms and HRQOL. A holistic meditation (HOME) intervention that combines mindfulness, compassionate meditation, and self-management may reduce psychosocial distress. Purpose: The aims of this study were to examine the feasibility and acceptability of the HOME intervention in patients with HF and to obtain preliminary data about its effects on psychosocial factors (depressive symptoms, perceived control, and social support), HF symptoms, and HRQOL. Methods: Weekly 90-minute intervention sessions were delivered to 11 patients with HF for 12 weeks. Data on feasibility and acceptability were collected for 12 weeks, and data on psychosocial factors, HF symptoms, and HRQOL were collected at baseline and after the intervention. Results: Eleven of 13 enrolled patients completed all intervention sessions; 2 withdrew because of family health issues. Mean acceptability scores for all sessions ranged from 98% to 100%. In paired t test analyses, perceived control (P = .02, Cohen d = 0.82) and social support (P = .008, Cohen d = 1.00) increased, severity of depressive symptoms (P < .001, Cohen d = 1.54) and HF symptoms (P < .001, Cohen d = 1.91) decreased, and HRQOL was improved (P < .001, Cohen d = 1.82). Conclusions: The HOME intervention was feasible and acceptable and had positive effects on psychosocial variables, HF symptoms, and HRQOL for patients with HF. Our results indicate that treatment effects should be tested in a larger, controlled clinical trial.