OBJECTIVES: To asses the cost-effectiveness of two initial management strategies for the general practitioner in dyspepsia. The two strategies investigated are prompt endoscopy and a Helicobacter pylori test-and-treat strategy. METHODS: Pharmacoeconomic data was gathered alongside the SENSE (Strategy: Endoscopy versus Serology)-study from 1998 up to 2001. Patients were randomized in the endoscopy (n=105) and test-and-treat (n=118) group. The costs were standardized costs for 1999. Quality of life was measured at inclusion and one year later, using the validated Dutch translation of the RAND-36 questionnaire. The results obtained were transformed into one overall score, in terms of Quality Adjusted Life Years (QALYs). An incremental cost-effectiveness ratio (ICER) was calculated as incremental cost of test-and-treat over early endoscopy per QALY gained. For estimating the uncertainty we calculated 95% uncertainty limits using parametric bootstrap with angular transformation. RESULTS: For the test-and-treat group the total costs per patient were 511.02€ and the number of QALYs gained was 0.074 per patient. For the endoscopy group this was 748.08€ and 0.064 QALYs gained. The point estimate of the ICER indicated cost-savings and QALYs gained. Parametric bootstrap uncertainty limits indicate cost-savings per QALY gained (75.7%) and cost savings per QALY lost ranging from 11970€ to infinity. CONCLUSIONS: According to our data, the Helicobacter test-and-treat strategy is more cost-effective than prompt endoscopy in the initial management of dyspepsia in general practice.