BACKGROUND: The purpose of this study was to assess the effectiveness of a disease management program (DMP) in heart failure (HF) on the incidence of HF hospitalizations and related costs in a real-world population-based setting. METHODS: Insuffisance CArdiaque en LORraine (ICALOR), a DMP for HF was established in 2006 in the French region of Lorraine. Patients were enrolled after an index HF hospitalization. They received educational and home-visit monitoring programs by HF-trained nurses. General physicians received automatic alerts about patients' significant clinical or biological changes. We used the ICALOR and the national diagnostic related group databases to conduct a comparison of time-series trends in HF hospitalizations in France. The economic impact was obtained using the national scale of costs in France. RESULTS: The median age of the 1222 patients recruited before 2010 was 76years, and 65% were male. Upon enrollment, patients essentially presented with NYHA class II (n=537, 48%) or class III (n=359, 32%) symptoms. One-year mortality rate was 20.3%. The implementation of the ICALOR program was associated with a reduction in HF hospitalizations in Lorraine estimated by an absolute difference between the number of hospitalizations observed in the Lorraine region and that expected had it been similar to that observed in the whole country of -7.19% in 2010. The estimated annual hospital cost saved by ICALOR was €1,927,648 in 2010. CONCLUSION: Coordinated DMP of HF might improve outcome cost-effectively when implemented in a real-world population setting, and was associated in Lorraine with a substantial modification of the trend of HF hospitalizations.