BACKGROUND: Heart failure (HF) self-care is a robust predictor of prognosis in HF patients. Cognitive impairment is a common comorbidity in HF patients and constitutes a major challenge to HF self-care. Mindfulness training (MT) has been shown to improve cognitive function and interoception, two components essential to promoting effective HF self-care. OBJECTIVES: The aims of the Mind Your Heart-II (MYH-II) study are to investigate the effects of MT on HF self-care via changes in cognitive function and interoception in patients with comorbid HF and cognitive impairment, and to study the process by which MT can improve cognitive function via vagal control. We hypothesize that MT will improve cognitive function, interoception, and vagal control, resulting in enhanced HF self-care, compared to control participants. METHODS: MYH-II is a mechanistic parallel phase II behavioral randomized controlled trial. We will enroll 176 English or Spanish-speaking patients with comorbid chronic HF and mild cognitive impairment. Participants will be randomized to either: (1) 8-week phone-delivered MT + Enhanced Usual Care (EUC), or (2) EUC alone. Participants will complete baseline, end-of-treatment (3 months), and follow-up (9 months) assessments. The primary outcome is cognitive function (NIH Toolbox Fluid Cognition Composite Score). Additional key outcomes include: interoception (heartbeat tracking task, Multidimensional Assessment of Interoceptive Awareness), HF self-care (Self-Care of Heart Failure Index v7.2), and vagal control (high-frequency heart rate variability). IMPLICATIONS: If study hypotheses are confirmed, phone-based MT may be a key tool for improving HF self-care, and possibly clinical outcomes, in HF patients with comorbid cognitive impairment.