Background: Patients with heart failure (HF) commonly remain symptomatic after medical treatment. Symptoms are associated with rehospitalizations and mortality. We developed a 6-month nutrition intervention targeting the 3 most common HF symptoms: edema, shortness of air, and fatigue. The intervention involves 3 nutrients that target the pathologic pathways underlying symptoms: sodium, omega-3 fatty acids, and lycopene. Hypothesis: Time to first event will be longer in the nutrition intervention group than in the placebo group at 1-year follow-up. Methods: This was a randomized controlled double-blind clinical trial where 118 patients (mean age 63±12 years; 40% female; 64% NYHA class III or IV) with HF were randomized to active intervention vs placebo groups. The active intervention included a skill-building strategy based on Theory of Planned Behavior using Motivational Interviewing. It included a low sodium (LS) diet (2500mg sodium/day), lycopene supplementation daily (8 ounces [oz] of LS sodium tomato juice or 11.5 oz of LS V8 juice), and omega-3 fatty acid capsules (350mg EPA, 50 mg DHA/capsule) 3/meal with each meal. Placebo patients received generic instructions to follow a LS diet, 8 oz/day of fruit juice with no lycopene (e.g. cranberry juice) and capsules that contained soybean oil, but that looked like intervention capsules. Cox proportional hazards modeling was done to determine time to event of cardiac hospitalization or death based on intervention group. Models were adjusted for age, gender, NYHA class and HF medications. Results: The two groups were similar at baseline. The active intervention group had better event-free survival (Figure, p = 0.03) independent of covariates. Placebo patients were 2.2 (95% CI 1.025 - 4.584) times more likely to experience an event. Conclusion: A diet-based intervention aimed at the pathologic pathways underlying the 3 most common HF symptoms is successful in reducing cardiac rehospitalizations and mortality.