(1) Background Adherence to treatment guidelines in heart failure (HF) patients is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Introducing hybrid comprehensive telerehabilitation (HCTR) consisting of telecare, telerehabilitation, and remote monitoring of implantable devices might be an option to improve adherence to recommendation and can affect the prognosis. The purpose is to investigate the association of adherence to HCTR with mortality and hospitalization. (2) Methods This analysis formed part of TELEREH-HF multi-center, randomized trial that enrolled 850HF patients (NYHA I-III;LVEF ≤ 40%). Patients were randomized 1:1 to 9-week HCTR (1 week in hospital and 8 weeks at home) plus usual care or usual care only and followed-up for 14 to 26 months. This analysis focuses on the HCTR group. Adherent patients were those who adhered both to the number of training sessions prescribed and to the duration of the prescribed cycle by at least 80%; non-adherent patients were those who adhered<20% to the prescribed number of training sessions and their duration. The remaining patients were classified as partially adherent. (3) Results There were 350 (88.4%) adherent patients, 39 (9.8%) partially adherent patients, and 7 (1.8%) non-adherent patients. There were 46 deaths during follow-up. Non-adherence or partial adherence was associated with higher risk of cardiovascular (CV) mortality (hazard ratio (HR) = 2.62, p = 0.021); all-cause mortality or HF hospitalization (HR = 1.71, p = 0.038); CV mortality or HF hospitalization (HR = 1.89, p = 0.014). (4) Conclusions The adherence to HCTR was high. Adherence to HCTR was associated with improved prognosis for CV mortality and the reduction in the combined outcome of CV mortality or HF hospitalization.