Background: Lansoprazole, a substituted benzimidazole, is a proton pump inhibitor which is highly effective in the control of 24‐h intragastric acidity. The aim of this multicentre, randomized, double‐blind study was to compare lansoprazole 30 mg once daily and omeprazole 20 mg once daily in the symptom relief and healing of patients with reflux oesophagitis. Methods: Six hundred and four patients with endoscopically proven oesophagitis and a recent history of heartburn were randomly assigned to receive lansoprazole 30 mg or omeprazole 20 mg daily for 4–8 weeks. Daily assessment of symptoms was made by the patient using a 100‐mm Visual Analogue Scale. Clinical symptoms were evaluated at weeks 0, 1, 4 and 8. Endoscopic assessment of healing, defined by normalization of the oesophageal mucosal appearance, was made at weeks 4 and 8. Results: Two hundred and eighty‐two patients in the lansoprazole group and 283 patients in the omeprazole group were eligible for inclusion in the per protocol analysis. At 3 days, there was a significant improvement in daytime symptoms of heartburn for patients in the lansoprazole group compared with the omeprazole group (P=0.05). A similar but non‐significant trend was seen at 7 days (P=0.18). Clinical assessment at 7 days demonstrated significant improvement in daytime epigastric pain in the lansoprazole group compared with the omeprazole group (P=0.03), with a similar but non‐significant trend in night‐time epigastric pain (P=0.07). Healing rates of oesophagitis at 4 and 8 weeks were 70 and 87%, respectively, with lansoprazole, and 63 and 82%, respectively, with omeprazole. Logistic regression analysis of the cumulative healing rates, which included baseline factors affecting outcome, resulted in an odds ratio of 1.46 (95% CI=0.87–2.45), suggesting a higher chance of being healed with lansoprazole treatment compared with omeprazole treatment. A total of 615 adverse events were reported by 308 (51%) patients during the study period. The majority of events were mild in nature and the incidence was similar in both treatment groups. The most frequently reported events were headache, diarrhoea and nausea. Conclusion: Lansoprazole provides greater symptom relief compared with omeprazole during the first week of treatment. Both treatments were effective in healing oesophagitis.