We evaluated the results of a 12-month treatment using different regimens of omeprazole at the dose of 20 mg daily (three day week-end treatments and every other day) and of 150 mg nocte of ranitidine on Helicobacter pylori status and on preventing duodenal ulcer relapses in 140 Helicobacter pylori positive patients with healed duodenal ulcer. Only every-other-day omeprazole suppresses Helicobacter pylori after 3 month therapy (p < 0.001), after 6 months (p < 0.001) and 12 months (p < 0.05). After 3 months (T1) no significant effectiveness was found in the prevention of ulcer relapses by omeprazole and ranitidine. After 6 months (T2) a significant reduction of relapses (p < 0.05) was recorded when comparing every- other-day omeprazole to the weekend regimen. After 12 months every-other-day omeprazole treatment significantly reduced the relapses compared with the week-end therapy (p = 0.05) and with ranitidine (p < 0.05).