Background: Investigators have noted an intervention’s absolute benefits depend on the baseline risk of outcome in the treated population. But baseline risks of clinic-based patients in trials are often higher than that of community-based samples, potentially leading to optimistic estimates of benefit and cost-effectiveness. However, within community samples there are subgroups who have sufficiently high baseline risk that their anticipated absolute risk reduction merits consideration (e.g. smaller number needed to treat (NNT)); a prognostic risk-score is one approach to identifying these risk groups. Objectives: Using estimates of benefit (hospitalizations averted, RR 0.74, 95%CI 0.63,0.87) from a previously published systematic review of heart failure (HF) management, we estimated a program’s efficiency based on differing levels of predicted risk. Methods: Comprehensive longitudinal medical history and demographic data on HF patients from a large integrated US health plan were used to build a prognostic risk-score for cardiovascular-related hospitalization over 1-year. To maximize applicability we evaluated clinical findings that are easily retrievable using electronic data systems. Hospitalization costs came from Medicare data. We present two scenarios: one targeting highest risk patients (top 20%), and one without targeting (all patients). Our main findings are expressed as the NNT to avoid a hospitalization. We also calculated the program’s potential dollar savings from averting hospitalizations, assuming an annual intervention cost of USD 700 per year. Results: The average risk for hospitalization in the systematic review’s trials was 45% (NNT = 9); our population’s average risk was 18% (NNT = 21); predicted risk among the highest risk patients was 33% (NNT = 11). After accounting for the intervention cost, the base-case analysis shows a savings of USD 122/patient at highest risk. Failing to intervene according to predicted risk (no targeting) would actually cost USD 211/patient. Conclusions: Systematic reviews have shown that HF management programs are effective for patients in clinic-based samples. Our findings illustrate how results from systematic reviews can be integrated into community-settings by using a prognostic risk score to focus attention on high-risk subgroups, thereby maximizing efficiency.