OBJECTIVE: To compare the cost-effectiveness of esomeprazole 40 mg od or omeprazole 20 mg od in the acute treatment of patients with reflux oesophagitis in Greece. METHODS: A simple decision analysis model was designed to compare the cost-effectiveness of esomeprazole vs. omeprazole during eight weeks' acute treatment of reflux oesophagitis patients. Omeprazole, the leading PPI in Greece, was chosen as the comparator. Probability of treatment success was based on pooled healing rates (Life Table estimates) from 3 clinical studies (N=4877). Only direct medical costs were included in the cost-effectiveness analysis. As patients can unrestrictedly visit public or private sector GPs or gastroenterologists, all patients were assumed to visit a specialist. An endoscopy was assumed to be carried out in non-responders after eight weeks' of therapy, which is a conservative patient management assumption, according to results obtained from a market research among Greek gastroenterologists. Furthermore, the analysis did not consider additional treatment costs (e.g. drugs, visits) for failures beyond eight weeks. One analysis was carried out by using private market and one by using public hospital endoscopy and visit charges. RESULTS: Healing rates from the pooled analysis showed that esomeprazole is significantly more effective than omeprazole. After 4 weeks of therapy, healing rates were 77.7% for esomeprazole compared with 67.6% for omeprazole (p<0.001). The corresponding values after 8 weeks treatment were 93.4% and 86.2%, respectively (p<0.001). The decision analysis model resulted in similar direct medical costs for the esomeprazole and the omeprazole strategy, both when using public (€328 vs. €330) and private charges (€353 vs. €356). CONCLUSIONS: Despite using conservative assumptions, esomeprazole 40mg od was found to be cost-effective compared with omeprazole 20mg od in the acute treatment of patients with reflux oesophagitis in Greece, since esomeprazole provides better effectiveness at no additional treatment costs.