OBJECTIVES: Chronic heart failure (CHF) is a major health issue because of its growing prevalence, morbimortality and associated resource consumption. Beta blockers have been shown to be effective and cost-effective therapies for CHF. The aim is determining what beta blocker constitutes the most efficient therapy for CHF patients in Spain. METHODS: Systematic review of primary (clinical trials) and secondary (meta-analyses, clinical practice guidelines and economic assessments) evidence on beta blockers for CHF issued before May 2012. Once that efficacy of each beta blocker was established, local drug databases were accessed in order to estimate the updated annual cost of each therapy and daily dose in Spain. RESULTS: Given their similar efficacy [death RR: bisoprolol: 0.66, p<0.0001; metoprolol: 0.66, p<0.0001; carvedilol: 0.65, p<0.005, nebivolol: 0.88, p=0.21] and safety profiles, international clinical guidelines on Cardiology recommend bisoprolol, metoprolol succinate, carvedilol and nebivolol as first choice therapies for CHF (class I and level of evidence A). Annual treatment costs per patient reached 38.70€; 162.53-311.69€; 170.70€ and 188.14€ for bisoprolol, carvedilol, metoprolol succinate and nebivolol, respectively. When hospitalization costs are considered, cost per avoided death was 9.512€, 14.989€, 16.767€ and 50.795€ for bisoprolol, carvedilol, metoprolol succinate and nebivolol, respectively. Results of the cost-benefit analysis indicated that only bisoprolol showed a net benefit, with an estimated annual savings of 116.293€. Budget impact analysis yields that bisoprolol implies a saving of 76-88% of carvedilol cost of therapy per year and patient, 77% when compared to metoprolol succinate and 79% versus nebivolol. CONCLUSIONS: Despite the underuse of betablockers for CHF treatment, they have demonstrated to be effective and cost-effective. Among them, bisoprolol gathers pharmacologic, legal and pharmacoeconomic characteristics that confirm their being the most efficient beta blocker (both in terms of cost-benefit and cost-effectiveness) for CHF patients in Spain.