OBJECTIVES: Genetic testing prevents sudden cardiac death (SCD) in asymptomatic first-degree relatives of patients with established inherited cardiopathies. The objective is to estimate the cost-effectiveness of conducting genetic testing in first-degree relatives of patients with Hypertrophic Cardiomyopathy (HCM), Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Long-QT Syndrome (LQTS), Brugada Syndrome (BrS) or Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). METHODS: A Markov model was developed to determine the cost per life-year gained (LYG) and the symptom-free years (SFY) gained of using genetic testing in first-degree relatives at risk of SCD due to gene-related cardiopathies. The comparator was real world clinical practice (with no genetic testing). Four health states were defined: 1) Asymptomatic; 2) Minor event; 3) Major event; and 4) Death. The model was populated with data derived from the literature, local sources of input costs and resources use, and expert opinion. The analysis was conducted from the Spanish Health System (NHS) and social perspective in a hypothetical cohort of 1,000 patients followed over their lifetime. All costs referred to €,2012. Univariate and probabilistic sensitivity analysis were performed. RESULTS: The mean cost per patient with genetic testing compared to usual practice was € 51,374 vs. € 72,611 for HCM, € 58,454 vs. € 80,337 for ARVC, € 20,575 vs. € 21,659 for LQTS, € 38,005 vs. € 60,307 for BrS, and 28,286 vs. € 37,519 for CPTV, respectively. In the case of LQTS and CPTV, genetic testing implied a mean increase in LYG of 0.96 and 0.04 years per patient, respectively. Genetic testing was dominant for LQTS and CPTV and regarding HCM, ARVC and BrS was almost equally effective and less costly compared with usual practice. Sensitivity analyses confirmed the consistency of results. CONCLUSIONS: Compared to current practice with no screening, genetic testing in first-degree relatives at risk of SCD is cost-effective for HCM, ARVC, BrS, CPTV and LQTS in Spain.