Abstract Background Impact of telemedicine on heart failure outcomes has shown conflicting results. Little is known about the effect of these programs on mid-term healthcare costs. Purpose To evaluate the cost-efficacy of a comprehensive telemonitoring program within the vulnerable post-discharge period after an acute heart failure admission. Methods The insuficiència cardiaca Optimizació Remota (iCOR) trial was a single-centre, randomized, open-label study designed to evaluate the efficacy of the addition of telemonitoring and teleintervention to a specialized multidisciplinary nurse-led heart failure (HF) program. Adult patients with a recent hospital admission for acute HF and an acceptable social support and cognitive ability were recruited. This sub-analysis evaluates the effect of telemedicine on mid-term healthcare costs, including clinical events, drugs and devices, technology purchase and maintenance, outpatient care, days of hospitalization, procedures and complementary tests. t-test via bootstrap estimation is used to compare differences between the telemedicine (TM) and the usual care (UC) groups. Results 81 patients were assigned to the TM group and 97 patients to the UC group. Mean age was 74 years, more than 50% had HF with preserved ejection fraction and 25% were frail. Baseline characteristics were well-balanced between groups. Among the TM subgroup, adherence was very high (< 1% of missed biometric daily transmissions). During 6 months of follow-up, mean total healthcare cost per patient was 7949 euros (€) in the UC cohort and 4383 € in the TM cohort (relative risk reduction [RRR] of 45%; between-group differences 3546 €, 95% confidence interval 627-6464 €, bootstrap achieved significance level 0.022). This result was consistent across several subgroups (age, sex, frailty, left ventricular ejection fraction, educational level) and mainly driven by a 63% RRR in costs of hospitalization (which accounted for two-thirds of the total costs) in the TM cohort. 20 patients required HF admissions in the TM group, compared to 51 patients in the TM group (p < 0.001). This was associated with a 59% RRR in the need for diagnostic procedures. Total number of days of hospitalization per patient decreased from 12.2 in the UC group to 4.2 days in the TM group (p = 0.003), impelled by a reduction in HF and cardiovascular days of hospital stay. On the contrary, ambulatory care costs increase two-fold in the TM group compared to UC group. Nevertheless, these costs only accounted for a 19% of the total costs. Cost of devices needed to implement TM supposed 698 € per patient. Use of TM was associated with a 355 € increase in the cost of ambulatory neurohormonal treatment for HF. Conclusions TM implementation during the vulnerable phase after an acute HF admission was associated to a 45% RR reduction in mean total healthcare cost per patient. This result was driven by an almost two-thirds decrease in costs of hospitalization.UC and TM total healthcare costs