OBJECTIVES: To assess cost-effectiveness of esomeprazole 40mg once daily (od) versus generic omeprazole 20mg od in the acute treatment of reflux esophagitis (RE) in Germany. METHODS: A decision analysis model was used considering pooled effectiveness data on 8 weeks treatment of RE from three large, randomised, double-blind comparative clinical studies (n = 4877). Results were analysed using an 8-week time horizon and reported separately, including work productivity costs or direct medical costs (drugs, physician contacts, investigations) only. Utility values associated with having healed RE (0.84) or unhealed RE (0.69) were derived from a survey (n = 1011) using the rating scale method in patients with gastroesophageal reflux disease (GERD). Estimates of GERD-related work productivity loss (absence from work and reduced productivity while at work) were derived from observed differences in productivity before and after treatment with esomeprazole in an open-label clinical study (n = 237). A probabilistic sensitivity analysis (PSA) on direct medical costs was used to assess robustness of results, along with additional analyses extending the time horizon beyond 8 weeks. An acceptable threshold of €50,000 per quality-adjusted life year (QALY) gained was used in the PSA. RESULTS: When including direct medical costs only, the analysis resulted in mean additional costs of around €13,000 per QALY gained by using the more effective esomeprazole treatment strategy. The PSA on the probability of esomeprazole treatment being below a threshold of €50,000 per QALY gained supported robustness of a conclusion that esomeprazole treatment is cost-effective (incremental cost-effectiveness ratio CONCLUSIONS: Esomeprazole 40mg od is cost-effective compared with generic omeprazole 20mg od in the acute treatment of RE in Germany.