Objective: To assess the long-term cost-effectiveness of two multidisciplinary management programs for elderly patients hospitalized with chronic heart failure (CHF) and how it is influenced by patient characteristics. Methods: A trial-based analysis was conducted alongside a randomized controlled trial of 280 elderly patients with CHF discharged to home from three Australian tertiary hospitals. Two interventions were compared: home-based intervention (HBI) that involved home visiting with community-based care versus specialized clinic-based intervention (CBI). Bootstrapped incremental cost–utility ratios were computed based on qualityadjusted life-years (QALYs) and total healthcare costs. Cost-effectiveness acceptability curves were constructed based on incremental net monetary benefit (NMB). We performed multiple linear regression to explore which patient characteristics may impact patient-level NMB. Results: During median follow-up of 3.2 years, HBI was associated with slightly higher QALYs (+0.26 years per person; p = 0.078) and lower total healthcare costs (AU$ −13,100 per person; p = 0.025) mainly driven by significantly reduced duration of all-cause hospital stay (−10 days; p = 0.006). At a willingness-to-pay threshold of AU$ 50,000 per additional QALY, the probability of HBI being better-valued was 96% and the incremental NMB of HBI was AU$ 24,342 (discounted, 5%). The variables associated with increased NMB were HBI (vs. CBI), lower Charlson Comorbidity Index, no hyponatremia, fewer months of HF, fewer prior HF admissions b1 year and a higher patient's self-care confidence. HBI's net benefit further increased in those with fewer comorbidities, a lower self-care confidence or no hyponatremia. Conclusions: Compared with CBI, HBI is likely to be cost-effective in elderly CHF patients with significant comorbidity.