Many endoscopically controlled comparisons with H2-blockers have widely documented that site- and cytoprotective drugs constitute effective and safe agents for the short-term treatment of gastric and duodenal ulcer. Their efficacy however, is counter-acted by the need for multiple daily administration which requires greater patient compliance. Due to its ability to eradicate Helicobacter pylori (HP) from the gastric antrum and retard relapses, colloidal bismuth may be the first choice anti-ulcer drug for those HP positive patients who do not accept continuous maintenance treatment after healing. A specific subgroup of duodenal ulcer patients who may particularly benefit from a short-term treatment with such agents (namely colloidal bismuth) are the non-responders to an 8-week course of H2-antagonists; conversely, actual evidence does not support the hypothetical superiority of such agents over H2-blockers in the treatment of cigarette smokers or chronic consumers of NSAIDs.