Korea and Japan show the highest incidence of gastric cancer and Helicobacter pylori infection. New 2013 guidelines on H. pylori infection differ between the two countries with regard to the indications for H. pylori eradication, diagnostic methods, and treatment regimens. Indications for eradication in Korean guideline focus on specific diseases such as peptic ulcer disease, low-grade gastric mucosa-associated lymphoid tissue lymphoma, and after resection of early gastric cancer, while Japanese guideline includes all H. pylori-associated gastritis for the prevention of dissemination. With regard to the diagnosis, either noninvasive or invasive method (except for bacterial culture) is recommended in Korea, while two noninvasive tests including serum anti-H. pylori IgG antibody level are preferred in Japan. As for the treatment regimens, second-line treatment (quadruple bismuth-containing regimen) is recommended without first-line triple therapy in areas of high clarithromycin resistance in Korea. However, there is no bismuth-based second-line treatment in Japan, and the Japanese regimen consists of a lower dose of antibiotics for a shorter duration (7 days). Such discrepancies between the two countries are based not only on the differences in the literature search and interpretation, but also on the different approvals granted by the national health insurance system, manufacturing process of the antibiotics, and diagnostic techniques in each country. Collaborations are required to minimize the discrepancies between the two countries based on cost-effectiveness.