Departmental sources Background: The aims of the present study were to determine whether a nurse-led program of care can improve medication adherence, quality of life (QoL), rates of rehospitalization, and all-cause mortality for chronic heart failure (CHF) patients. Material/Methods: CHF patients were randomly assigned into either a control group or an intervention group. At 12 weeks, patients were followed up to evaluate the rate of medication adherence, QoL (as assessed by SF-12 physical and mental component score [PCS and MCS]), rehospitalization, and all-cause mortality. Results: We recruited 152 patients. No significant differences in demographics, comorbidities, CHF severity, or etiology at baseline were observed. At discharge, no significant differences in medications prescription, PCS (46 vs. 45), or MCS (55 vs. 56) were observed. However, at 12-week follow-up, compared to the control group, patients in the intervention group were more likely to keep on medications therapy, with a significantly higher use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker [73.8% vs. 59.7%], beta-blocker (62.5% vs. 51.4%), and aldosterone receptor antagonist (60% vs. 54.2%). Both PCS (35 vs. 40) and MCS (42 vs. 49) were also significantly lower in the control group versus the intervention groups (P<0.05). Patients in the control group had higher incident rate of rehospitalization (8.0% vs. 5.2% per person-week) than in the intervention group, with an incident rate ratio of 1.54 (95% confidence interval [CI]: 1.06-2.23). Conclusions: A nurse-led discharge program of care can be a cost-effective and feasible approach for management of CHF patients in China.