The economic evaluation of new medicines is increasingly important for pricing, registration and selection for use. A decision-analytic strategy was performed to assess the economic impact of antacids alone (phase I therapy), and in combination with either omeprazole, 20 mg once daily, or ranitidine, 150 mg twice daily, for patients with persistent, symptomatic gastro-oesophageal reflux disease of grade II or more (Savary-Miller classification). Data were obtained from published literature, an expert panel of gastroenterologists and actual payments by a private insurer in the USA. Over the 7-month period of the analysis, omeprazole reduced both symptoms and overall costs when compared with ranitidine or antacids. Consequently, the cost per symptom-free month was 43% lower with omeprazole than with ranitidine. Thus, omeprazole should be considered as the initial therapeutic approach for patients in whom phase I therapy fails.