The term refractory is applied to those ulcers that fail to heal despite 3 months of active treatment, recur within 1 year despite maintenance therapy with H 2-receptor antagonists, or, in the untreated state, persist without remission. Approximately 20–30% of ulcers fulfill 1 of these 3 criteria. Factors often associated with a refractory ulcer include large ulcer size, gastric outlet obstruction, hour-glass deformity, penetration, Candida infection, and cimetidine resistance. Incomplete healing of the ulcer and/or initial treatment with H 2-receptor antagonists may predispose to a refractory long-term course. Successful treatment of the refractory ulcer correlates more with duration of treatment than with the drug used. The more potent antisecretory agents, such as omeprazole, may be the drug of choice. The role of smoking and other environmental factors is not clear.