SUMMARYOne‐hundred and seventy‐one patients with endoscopically proven duodenal ulcers were allocated at random to double‐blind treatment with 10 or 20 mg of omeprazole in the morning for up to 4 weeks. Patients completed the study if ulcer healing and pain relief had occurred at 2 weeks. A total of 155 patients completed the trial. Patients treated with 20 mg of omeprazole daily responded significantly more rapidly than those treated with 10 mg of omeprazole daily (P<0.001; Cochran‐Mantel‐Haenszel test covering both time points), cumulative healing rates at 2 and 4 weeks were 74% (58/78) and 91% (71/78), respectively. The corresponding rates in the group treated with 10 mg daily were 48% (39/81) and 75% (58/77). Pain relief was again more pronounced during treatment with the larger dose (P<0.05; stratified Wilcoxon test). No major clinical or biochemical side effects were noted. An omeprazole dose of 20 mg daily is preferable to a lower dose for the treatment of duodenal ulcer disease in the s