AIMS: The aim of this study was to determine the effectiveness of a long-term, nurse-led, multidisciplinary programme of home/clinic visits in preventing progressive cardiac dysfunction in individuals at risk of developing de novo chronic heart failure (CHF). METHODS AND RESULTS: A pragmatic, single-centre (tertiary-referral hospital with specialist cardiological services), open-label, randomized controlled trial with blinded endpoint adjudication was carried out. In total, 624 cardiac inpatients (66 ± 11 years, 71% male, and 70% with CAD) were randomly allocated (1:1) to standard care or the study intervention. The intention-to-treat cohort comprised 310 standard care and 301 intervention participants. During 51.0 ± 8.2 months follow-up, 38/310 (12%) standard care [mean event-free survival 1865 days, 95% confidence interval (CI) 1817-1913 days] vs. 41/301 (14%) intervention participants (1855 days, 95% CI 1804-1906 days) experienced the primary composite endpoint of de novo CHF hospitalization or all-cause mortality (P = 0.574). Although there were no statistically significant differences in the rate of cardiovascular-related and emergency hospitalizations, the NIL-CHF (Nurse-led Intervention for Less Chronic Heart Failure) group accumulated 478 (0.214 ± 0.70 vs. 0.095 ± 0.284 days/participant/month; P = 0.052) and 1097 fewer days of hospital stay (0.391 ± 1.80 vs. 0.199 ± 0.47 days/participant/month; P = 0.023), respectively, compared with standard care. The intervention group also showed better cardiac recovery on echocardiography at 3 years [81/226 (35.8%) vs. 56/225 (24.9%), odds ratio 1.44, 95% CI 1.08-1.92, P = 0.011]. CONCLUSIONS: Relative to a high level of standard care, the NIL-CHF intervention was ineffective in preventing CHF and rehospitalization. On the other hand, it was associated with reduced hospital stay and improved cardiac function over the long term. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (No. 12608000022369). © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.