Non-erosive reflux disease(NERD) is a common condition and acid-suppressing agents are the mainstay of treatment. A cost-effectiveness analysis comparing a PPI, lansoprazole (LPZ) and a H2RA, ranitidine (RAN) for the treatment of NERD in Japan was performed using a decision analysis. The time period studied was one month and payer or patient' s perspective was considered. Efficacy data were estimated from a randomized clinical trial. Expected days without symptom (healthy days) were 20 for LPZ 15 mg/day and 16 for RAN 300 mg/day. Direct costs were 4,750 yen for LPZ and 4,358 yen for RAN. Cost-effectiveness ratio (direct costs/healthy days) was 238 yen for LPZ and 272 yen for RAN. Considering the results from a large-scale survey of GERD patients in Japan, the slightly higher price of LPZ was outweighed by its greater efficacy, also from the patient's willingness to pay perspective. Lansoprazole was superior to ranitidine with regard to both efficacy and cost-effectiveness and therefore is the preferred therapeutic agent for treatment of NERD.