There are no generally accepted regimens for the treatment of H. pylori infection in patients with gastritis or duodenal ulcers. However, metronidazole based regimens have been reported to be among the most successful. Resistance to metronidazole, clarithromycin, and amoxicillin was determined for 46 clinical isolates of Helicobacter pylori in Saudi Arabia and tested by E test. Of these isolates, 69.5% was resistant to metronidazole (MIC > 8 mg/l), 21 % to clarithromycin (MIC > 1 mg/l) and 11 % were multiresistant. No resistance to amoxicillin was observed. Resistance to metronidazole was more common in isolates from females than in those form males. In conclusion, the present study demonstrates high metronidazole resistance rate of H. pylori isolates in Saudi Arabia. Regimens containing metronidazole are best avoided. Trials to test other antimicrobial combinations are recommended.