BACKGROUND: Although primary resistance to metronidazole remains high (56,8%), it is more widely used than clarithromycin as a firstline Helicobacter pylori (H. pylori) treatment in the common Tunisian practice. AIM: To compare the eradication rate in two protocols including clarithromycin versus metronidazole in Tunisian adults. METHODS: From July 2005 to December 2007, 85 patients aged 18 to 75 years presenting with gastro-duodenal lesions with H. pylori infection and requiring its eradication were included in the study. They were randomized to receive alternatively a seven-day triple therapy including: Omeprazole + Amoxicillin + Clarithromycin (OAC group) or Metronidazole (OAM group) twice a day. A second endoscopy with new biopsies was carried out 6 weeks after treatment to control eradication. RESULTS: Eighty five patients finished the protocol. The OAC and OAM groups included 46 and 39 patients respectively. They were comparable with respect to age, gender, clinical presentation and initial lesions. The total eradication rate was 60%. It was significantly higher in the clarithromycin group (69.6%) than in the metronidazole group (48.7%): p < 0.05. CONCLUSION: Clarithromycin is more effective than metronidazole in H. pylori eradication. It should be made available in our hospital's nomenclature. This would prevent iterative eradication courses and probably reduce treatment cost.