Many studies have investigated gender disparity in scientific publications, but this has been poorly studied in the field of digestive diseases. This study aimed to determine the gender difference of first and senior authors in publications related to Helicobacter pylori (H. pylori) during the past 20 years. Data were derived from original articles published in the main journals of digestive diseases (Journal of Hepatology, Gut, Gastroenterology, American Journal of Gastroenterology, Endoscopy, Gastrointestinal Endoscopy, Alimentary Pharmacology and Therapeutics, Digestive Endoscopy, Journal of Gastroenterology, Helicobacter, and Gastric Cancer) in 2000, 2005, 2010, 2015, and 2020. These original articles were classified according to the gender and nationality of the first and senior (last listed) authors. Linear-by-linear association test was used to analyze the proportion of women authors over time. Multivariable logistic regression was applied to explain the factors impacting authorship difference of first and senior authors. A total of 561 original articles on H. pylori were collected for this study, accounting for 10.70% in 2000 to 7.60% in 2020 among all articles. In these original articles, the percentage of women first authors increased from 14.60% in 2000 to 45.0% in 2020 (P < .001). The percentage of women senior authors increased from 5.60% in 2000 to 18.80% in 2020 (P < .001). Women first authors were more likely to perform research with women senior authors (18.42%) than with men senior authors (10.23%, P < .001). The proportion of women first authors from Oceania were higher than that from North and South America (P = .004), whereas there was no statistical difference regarding women senior authors. In the past 2 decades, although the percentage of women authors among both first and senior authors in the field of H. pylori research has increased significantly, women are still a minority in original research.