The effectiveness of heart failure management in clinical practice is limited by physicians' suboptimal utilization of effective medications, patients' poor adherence to dietary sodium limitation and optimal drug therapy, and the lack of systematic monitoring of patients after hospitalization. The present study evaluated the feasibility and safety of MULTIFIT, a physician-supervised, nurse-mediated, home-based system for heart failure management that implements consensus guidelines for pharmacologic and dietary therapy using a nurse manager to enhance dietary and pharmacologic adherence and to monitor clinical status by frequent telephone contact. Fifty-one patients with the clinical diagnosis of heart failure were followed for 138 +/- 44 days. Daily dietary sodium intake fell by 38%, from 3,393 to 2,088 mg (p = 0.0001); average daily medication doses increased significantly (lisinopril: 17 to 23 mg, p <0.001; hydralazine: 140 to 252 mg, p = 0.01). Functional status and exercise capacity improved significantly (p = 0.01). Compared with the 6 months before enrollment and normalized for variable follow-up, the frequency of general medical and cardiology visits declined by 23% and 31%, respectively (both p <0.03); emergency room visits for heart failure and for all causes declined 67% and 53%, respectively (both p <0.001). Hospitalization rates for heart failure and for all causes declined 87% and 74%, respectively (p = 0.001), compared with the year before enrollment. The MULTIFIT system enhanced the effectiveness of pharmacologic and dietary therapy for heart failure in clinical practice, improving clinical outcomes and reducing medical resource utilization.