Background-Previous evaluations of the cost eVectiveness of antireflux medication used in gastro-oesophageal reflux disease (GORD) have been based on results obtained in controlled clinical trials. Unfortunately such an approach does not necessarily identify the therapeutic option which provides the greatest benefit from available resources in real life situations. To make an informed choice requires a recognition that the costs and benefits of therapy in practice may diVer from those identified in trials. Aims-To evaluate, based on a retrospective prescription database analysis, the cost eVectiveness of alternative treatment options for patients with uncomplicated GORD. The analysis assesses health service resource use during the first six months of treatment in three groups of patients initially prescribed cisapride (CIS), ranitidine (RAN), or omeprazole (OME). Methods-The MediPlus™ UK database was used to identify all health care resources consumed by patients in the three treatment groups during their first six months of treatment. Patients with more complicated GORD, as indicated by initial referral to a specialist or outpatient hospital visit (<13%), were excluded from the analysis. Results-The average cost per patient for the initial six months of treatment for CIS, RAN, and OME based therapies was £136, £177, and £189 per patient, respectively. A major element underlying this cost variation was the acquisition cost and quantity of antireflux medication required by patients. The average number of one month equivalent prescriptions consumed during this six month period was 1.85 (CIS), 2.57 (RAN), and 2.96 (OME) with associated costs of £49 (CIS), £67 (RAN), and £105 (OME). Antacid and alginate/antacid use was higher in the CIS and RAN groups (about 1.0 antacid prescription per patient versus 0.4 for OME), but their contribution to the total cost per patient was less than 2%. The number of general practitioner consultations over the six month period for each treatment group was 2.4 (CIS), 2.9 (RAN), and 2.6 (OME) with associated costs of £60.31 (CIS), £73.06 (RAN), and £65.52 (OME). The average number of non-drug interventions (referrals, outpatient visits, endoscopies, barium meals, or x rays) was 0.34 in the RAN group compared with less than 0.2 in the CIS and OME groups. The costs associated with such interventions were £23.80 (RAN), £9.60 (CIS), and £11.10 (OME) per patient. Conclusion-The data indicate that the "step up" approach, starting with a prokinetic or H 2 receptor antagonist, represents the most cost eVective initial therapeutic strategy for a primary care physician to adopt when faced with a patient with first diagnosis of uncomplicated GORD. (Gut 1998;42:13-16)