OBJECTIVES: Determine which new generation proton pump inhibitor (PPI) is most cost-effective in the maintenance phase of patients with C & D esophagitis as well as their expected impact on Spanish NHS budget. METHODS: A pharmacoeconomic deterministic model, NHS perspective, was developed to compare esomeprazole (ESO40mg/d), lansoprazole (LANSO30mg/d) and pantoprazole (PANTO40mg/d) in the maintenance phase of patients with C&D esophaghitis.. The effectiveness measure considered was symptoms free-days after 12 months of treatment. And the costs included were drugs and health care utilization resources (diagnostic methods, physicians visits and surgery), expressed as 2006 €. Moreover a budget impact model was done to know the affordability of most cost-effective drug utilization in a 1,000 patients cohort. RESULTS: ESO provide higher remission rates (308 days without symptoms) than the other alternatives: LANSO-231 days; PANTO-270 days. The annual cost by patient are: 794€-ESO, 885€-LANSO, 772€-PANTO. The analysis indicates that ESO being a dominant therapy vs. LANSO; and vs. PANTO presents an incremental cost-effectiveness ratio of 0.59 €/day. The expected cost by patient is 822.32€ (259 symptoms free-days), based on 2006 treatment patterns. Increasing the ESO utilization on 25, 50, 75 & 100%, instead of less effective and costly drugs, could produce potential savings for the Spanish NHS: 1370€, 2850€, 4120€ & 6190€, respectively; which would allow treatment of more patients with the same budget: 2, 3, 5 and 8 additional patients, correspondingly. CONCLUSION: ESO is the most cost-effective and efficient PPI in for treatment of patients for the maintenance of C&D esophaghitis treatment in Spain.