Introduction In Northern Sardinia, one-week triple standard therapies containing a proton-pump inhibitor and two antibiotics for H.pylori infection have an average cure rate of 57% largely due to a high prevalence of antimicrobial resistance. The efficacy of miocamycin-containing treatment for 10days was evaluated. Materials and Methods Patients referred to the endoscopy service for dyspeptic symptoms were enrolled. H. pylori infection was defined as a positive rapid urease test, presence of the bacteria on gastric biopsies, and a positive 13C-UBT. Treatment consisted of 10days with omeprazole 20mg, miocamycin water-soluble 900mg, and tinidazole 500mg all bid. Success was evaluated 40-50days after the end of therapy and defined by a negative 13C-UBT. Compliance was considered good if at least 90% of the total number of the pills were taken. Fluorescent in situ hybridization (FISH) technique was applied on paraffin-embedded gastric tissue sections to test susceptibility to clarithromycin of the bacteria. Results 50 patients were enrolled (mean age; 52, 36% men). Miocamycin-containing therapy cured 86% (42/49; 95% CI=72-94%) of infected patients by PP analysis. Susceptibility data (FISH) was available for 38 patients. Cure rates for the 28 with clarithromycin-susceptible infection was 96% vs 50% for those with resistant or mixed infection, (p=.003). Good compliance was recorded in 48 patients. None of the patients discontinued therapy. Conclusions Miocamycin appears to be a valid alternative for clarithromycin for H.pylori eradication. Head-to-head studies will be needed to ascertain whether it is superior.