The role of telemedicine in the management of patients with chronic heart failure (HF) has not been fully elucidated. We hypothesized that multidisciplinary comprehensive HF care could achieve better results when it is delivered using telemedicine. In this study, 178 eligible patients with HF were randomized to either structured follow-up on the basis of face-to-face encounters (control group, 97 patients) or delivering health care using telemedicine (81 patients). Telemedicine included daily signs and symptoms based on telemonitoring and structured follow-up by means of video or audio-conference. The primary end-point was non-fatal HF events after six months of follow-up. The median age of the patients was 77 years, 41% were female, and 25% were frail patients. The hazard ratio for the primary end-point was 0.35 (95% confidence interval (CI), 0.20-0.59; p-value < 0.001) in favour of telemedicine. HF readmission (hazard ratio 0.39 (0.19-0.77); p-value=0.007) and cardiovascular readmission (hazard ratio 0.43 (0.23-0.80); p-value=0.008) were also reduced in the telemedicine group. Mortality was similar in both groups (telemedicine: 6.2% vs control: 12.4%, p-value > 0.05). The telemedicine group experienced a significant mean net reduction in direct hospital costs of €3546 per patient per six months of follow-up. Among patients managed in the setting of a comprehensive HF programme, the addition of telemedicine may result in better outcomes and reduction of costs.