Helicobacter pylori infection is associated with 95% of duodenal ulcers and more than 80% of gastric ulcers. Several reports have indicated that screening for H pylori may avoid subsequent endoscopic examination. We screened 183 dyspeptic patients, aged under 45, by taking a history of sinister symptoms and regular use of non-steroidal anti-inflammatory drugs (NSAIDs), together with serological testing for H pylori. Endoscopy was performed on 113 patients, of whom 90 (49%) were seropositive, 14 (8%) had sinister symptoms, and 9 (5%) had used NSAIDs regularly. In 34 (19%) patients we detected peptic ulceration. The remaining 70 (38%) patients who were H pylori seronegative, had no sinister symptoms, and had not taken NSAIDs (screen-negative), did not undergo endoscopy but were returned to their primary care physician for treatment of symptoms. At subsequent reassessment (of the non-endoscoped group), symptom severity (p = 0.002), interference with life events (p = 0.01), and medication (p = 0.0002) were all significantly lower in the 6 months after screening than in the 6 month period before screening. Only three screen-negative patients were re-referred after screening but their endoscopic findings were normal. Thus, 67 (36%) endoscopies were avoided. When the non-endoscoped screen-negative patients were compared with a cohort of endoscoped screen-negative patients, the groups did not differ in terms of symptom severity (odds ratio 1.12, 95% CI 0.53-2.35, p = 0.77) or interference with life events (0.82, 0.38-1.76, p-0.61). However, medication use was significantly less (0.37, 0.17-0.80, p = 0.01) in those who did not have an endoscopy. Our study indicates that colonisation screening based on H pylori serology, a history of sinister symptoms, or a history of NSAID use was worthwhile in dyspeptic patients. We avoided 37% of endoscopies and reduced drug usage without disadvantaging those not endoscoped.