In a double-blind, parallel-group clinical trial in 248 patients with symptomatic duodenal ulcers [97% greater than 5 mm diameter], 126 were randomized to receive omeprazole 20 mg once daily in the morning and 122 were randomized to receive ranitidine 300 mg once daily at night for 2 wk and if the ulcers were unhealed for a total of 4 wk. When ulcer healing was assessed on an intention-to-treat basis, 79% of those receiving omeprazole had healed ulcers after 2 wk compared with 62% of those receiving ranitidine (p less than 0.005; therapeutic gain for omeprazole, 18%; 95% confidence intervals, +6% to +29%). At 4 wk the figures were 91% (omeprazole) and 80% (ranitidine) (p less than 0.05). After 2 wk, 77% of omeprazole-treated and 59% of ranitidine-treated patients were free of ulcer pain (p = 0.005). Assessed by diary cards (successfully completed by 92% of patients), daytime pain resolved more quickly in omeprazole-treated patients than in those receiving ranitidine (p less than 0.01). Omeprazole-treated patients took fewer antacids (p less than 0.05) over the first 2 wk. Omeprazole, 20 mg each morning, provides more rapid relief of the symptoms of duodenal ulcer and heals a greater proportion of duodenal ulcers within 2 and 4 wk than ranitidine, 300 mg each night.