OBJECTIVES: The aim of this study was to combine clinical results from the REVERSE study (Resynchronisation reverses Remodelling in Systolic Left Ventricular Dysfunction) and costs associated with the addition of cardiac resynchronization therapy (CRT) to optimal medical therapy (OMT) in patients with mild symptomatic (NYHA I-II) or asymptomatic left ventricular dysfunction and markers of cardiac dyssynchrony in Spain. METHODS: We developed a Markov model of CRT + OMT (CRT-ON group) vs. OMT alone (CRT-OFF group) based on a retrospective cost-effectiveness analysis. Raw data from the model was derived from literature and expert opinion, reflecting clinical and economic consequences of patient’s management in Spain. Time horizon was 10 years, and costs were expressed in Euro 2010. Both costs and effects were discounted at 3% per annum. RESULTS: CRT-ON group showed higher total costs than CRT-OFF, however patients with CRT reduced 94% the length of hospitalization in the ICU (0.006 vs. 0.091 days) and 34% in general ward (0.705 vs. 1.076 days). Surviving patients with CRT-ON (88.2% vs. 77.5%) remained in slighter functional class longer and they achieved an improvement of 0.9 life years (LYGs) and 0.77 years quality-adjusted life years (QALYs). In terms of cost per LYGs, the results were €40,782 (5 years) and €18,431 (10 years), and in terms of costs per QALYs gained were €39,800 and €21,500 at 5 and 10 years respectively. Probabilistic sensitivity analysis showed that the probability of CRT-ON was cost-effective is 65.54% at 10 years. CONCLUSIONS: The use of CRT added to OMT represents an efficient use of resources in patients suffering from heart failure in NYHA functional class I and II, with cost-effectiveness ratios below the Spanish threshold at 10 years.