Omeprazole (20 mg od/b.d.), clarithromycin (250 mg b.d.) and tinidazole (500 mg b.d. for 7 days) [OCT] is an effective regimen against Helicobacter pylori. However, treatment fails in 5%-10% of patients and the reasons for this are not clear. We investigated patient factors that independently predicted failure of this regimen. H. pylori-positive patients were prescribed OCT and the success of treatment was evaluated by the 13C-urea breath test at least 4 weeks after completion of therapy. Patients were prospectively interviewed on past medical history of peptic ulcer and H2-receptor antagonist (H2RA) pre-treatment, smoking history, and alcohol intake. Data were also collected on age, gender, and endoscopic diagnosis to determine factors predicting failure of OCT. H. pylori eradication was achieved in 238 of 273 patients [87%-95% confidence intervals (CI), 83%-91%]. Age, alcohol intake, past medical history of peptic ulcer and peptic ulcer at endoscopy were not independently associated with treatment failure. H. pylori eradication with OCT was less successful in women (P = 0.02), in patients who had received H2RA pre-treatment (P = 0.02), and in smokers (P = 0.02) when evaluated by multiple logistic regression. These findings indicate that OCT is less effective in smokers and in patients who receive H2RA pre-treatment suggesting that these agents should be avoided, if possible, before the patient commences therapy. H. pylori eradication was less successful in women; this result needs further evaluation.