The aim of the present study was to determine the cost-efficiency of different duodenal ulcer disease treatment practices in Malaysia. Six Malaysian gastroenterologists met to discuss the direct costs related to Helicobacter pylori (HP) eradication treatment. Five treatment strategies were compared: (i) histamine H2 receptor antagonists (H2RA), acid suppression therapy for 6 weeks followed by maintenance therapy as needed; (ii) bismuth triple + proton pump inhibitor (PPI), bismuth (120 mg, q.i.d.), metronidazole (400 mg; t.i.d.), tetracycline (500 mg, q.i.d.) for 7 days and PPI, b.i.d., for 7 days; (iii) OAC, omeprazole (20 mg, b.i.d.), amoxycillin (1000 mg, b.i.d.) and clarithromycin (500 mg, b.i.d.) for 7 days; (iv) OMC, omeprazole (20mg, b.i.d.), metronidazole (400mg, b.i.d.) and clarithromycin (500 mg, b.i.d.) for 7 days; and (v) OAM, omeprazole (20 mg, b.i.d.), amoxycillin (1000 mg, b.i.d.) and metronidazole (400 mg, b.i.d.) for 7 days. A decision tree model was created to determine which therapy would be the most cost-effective. The model considered eradication rates, resistance to anti-microbial agents, compliance and cost implications of treatment regimens, physician visits and ulcer recurrences during a 1 year time period assumption. The H2RA maintenance therapy was the most expensive treatment at Malaysian Ringgit (MR) 2335, followed by bismuth triple therapy (MR 1839), OMC (MR 1786), OAM (MR 1775) and OAC, being the most cost-effective therapy, at MR 1679. In conclusion, HP eradication therapy is superior to H2RA maintenance therapy in the treatment of duodenal ulcer disease. Of the HP eradication regimens, OAC is the most cost-effective.