BACKGROUND/AIMS It is controversial whether pretreatment with a proton pump inhibitor (PPI) before Helicobacter pylori eradication treatment decreases the eradication rate. To determine the effects of pretreatment with lansoprazole alone, followed by an H. pylori eradication regimen (lansoprazole 30 mg, amoxicillin 750 mg and clarithromycin 200 mg twice daily for 1 week), on the eradication rate and quality of life (QoL) of the patient. METHODS Patients with H. pylori-positive peptic ulcer were randomly assigned to two groups. The patients received either lansoprazole (30 mg) once daily for 6-8 weeks before H. pylori eradication (group A), or eradication treatment and then lansoprazole (30 mg) for 6-8 weeks (group B). To assess the QoL of the patients, the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire was evaluated. RESULTS A total of 116 patients were enrolled. The cure rates were 78.9% in group A and 78.0% in group B. In both groups, GSRS analysis showed a significant improvement of the overall GSRS score at the assessment of eradication efficacy, compared to baseline; there was no difference between the groups. CONCLUSION With this H. pylori eradication regimen, there was no difference in the cure rates and QoL associated with PPI pretreatment.