Helicobacter pylori (H. pylori) is strongly associated with a wide spectrum of gastrointestinal diseases, such as duodenal or gastric ulcers and gastric cancer. Currently, the main treatment of H. pylori infection involves the use of a combination of antimicrobial agents such as amoxicillin, metronidazole and clarithromycin and proton pump inhibitors (PPIs). In many guidelines, triple therapy consisting of two antibiotics (amoxicillin/metronidazole and clarithromycin) and a PPI is used as the first treatment line. Unfortunately, the increased resistance of H. pylori to clarithromycin and metronidazole adversely affect the effectiveness of triple therapy and reduces the eradication rates to an unacceptable level. Several regimens have been proposed to replace standard triple therapy such as bismuth-containing quadruple therapy, sequential therapy, concomitant therapy, hybrid therapy and levofloxacin-based therapy. Many regimens are used as rescue therapy based on what was previously used in the treatment such as bismuth quadruple therapy, rifabutin triple therapy and levofloxacin-based therapies. However, due to the bacterial resistance to antibiotics that can limit the applicability of such regimens and because the resistance to amoxicillin is very low, high-dose dual therapy (HDDT) consisting of amoxicillin and a PPI has been proposed as an effective and safe first-line or rescue therapy.