Clinical studies have shown that bismuth-containing quadruple therapy given twice a day for 10 to 14 days is effective and safe in the treatment of Helicobacter pylori infection in Sardinia. However, bismuth is no longer available in Italy. To report the effectiveness and tolerability of pantoprazole 20 mg, tetracycline 500 mg, and metronidazole 500 mg given b.i.d. (with the midday and evening meals) for 10 days supplemented with Lactobacillus reuteri (DSM 17938) 10(8) cfu/tablet once a day for 20 days in patients treated in a routine daily practice setting. H pylori infection was defined as a positive gastric histopathology and/or 13C-Urea Breath Test (UBT) and/or stool antigen testing. Successful eradication was documented by 13C-UBT, and/or stool antigen assay at least 4 weeks post-therapy. Compliance and side effects were recorded after completing treatment. A total of 45 patients (10 men, 35 women; mean age 52.6 years) have completed the treatment regimen with the success rate of 93% (95% confidence interval = 85-99%). Compliance was excellent. Side effects were absent or generally mild.Proton pump inhibitor-tetracycline-metronidazole-L reuteri therapy provided high eradication rates with few side effects and therefore can safely replace bismuth in H pylori treatment. Further studies are needed that include susceptibility testing.