OBJECTIVES A live-attenuated vaccine aimed at preventing herpes zoster (HZ) and post-herpetic neuralgia (PHN) is available in Europe for immunocompetent adults aged ≥50 years. The study objective is to assess the incremental cost-effectiveness ratio (ICER) of a vaccination program for this population in Spain when compared against the current strategy of no-vaccination. METHODS A state-transition Markov model has been developed to simulate the natural history of HZ and PHN and the lifetime effects of vaccination. Several health states are defined including good health, HZ, PHN and death. HZ and PHN health states are divided to reflect pain severity. The Markov cycle was 1 month and lifetime horizon. The HZ vaccine lifetime duration (waning rate of 8.3%) and a PHN vaccine duration of 10 years. PHN proportion was obtained from Cebrián-Cuenca (2011) and adjusted to reflect the incidence of PHN among HZ patients with pain. The vaccine coverage rate estimated was 30%, considering discount rates of 3% for costs and utilities. The strength of the results was confirmed with a probabilistic analysis based on Monte Carlo simulation. RESULTS A vaccination strategy compared to a no-vaccination resulted in 12.659€/QALY and 11.926€/QALY under third-party payer perspective and societal perspective respectively for the population aged ≥50 years. ICERs were within the commonly accepted thresholds of 30.000£/QALY (36.000€/QALY) gained in the UK. Sensitivity analyses showed that the model was most sensitive to discount rates and duration of vaccine protection. The lowest ICER was observed for the 70-74 years age group (6.657€/QALY under third-party payer perspective). CONCLUSIONS In Spain, a shingles vaccination strategy in older population would be a cost-effective alternative in comparison with no vaccination, due to an ICER of 12.659€/QALY from the third-party payer perspective.