AbstractBackgroundHelicobacter pylori antibiotic resistance is an increasing problem worldwide. Pylera^® may be an option as salvage therapy.AimTo assess the effectiveness, safety, and tolerance of Pylera^® as a third‐line in clinical practice.Materials and MethodsThis was a multicenter, observational, prospective database study in four Spanish hospitals. Consecutive H. pylori‐infected individuals treated with Pylera^® and a proton‐pump inhibitor (PPI) were invited to participate if they had failed to respond to PPI‐clarithromycin‐amoxicillin as first‐line and to levofloxacin‐amoxicillin‐PPI as second‐line therapy. Eradication was tested 4‐8 weeks after Pylera^® using a C¹³‐urea breath test. Treatment‐related adverse effects (TRAEs) were assessed through a questionnaire and by reviewing databases. A questionnaire on patient satisfaction was completed in the last visit.ResultsOf 103 subjects fulfilling the selection criteria, 101 were included in the intention‐to‐treat (ITT) analysis and 97 in the per‐protocol (PP) analysis. A 10 day course was prescribed in all patients. Esomeprazole 40 mg b.i.d. was the most used PPI regimen (ITT=94.1%). Ninety‐seven individuals (ITT=96.04%) completed more than 90% of the treatment. Overall eradication rates were ITT=80.2% (95% confidence interval [CI]: 72.3%‐88.1%) and PP=84.4% (95% CI: 76.8%‐91.8%). One or more TRAEs were experienced by 67.3% (95% CI: 57.7%‐75.7%), all mild or moderate. TRAEs and the number of pills were the main complaints.ConclusionIn an area of high antibiotic resistance to H. pylori, 10‐day Pylera^® plus double‐dose PPI emerged as an alternative as third‐line therapy, although not achieving optimal eradication rates. TRAEs were common but were neither severe nor did they condition compliance.