BACKGROUND: It is 40 years since the discovery of Helicobacter pylori infection. Over that time major changes have occurred in esophagogastroduodenoscopy (EGD) findings. The aim of this review is to describe these changes, and the important role H. pylori infection has played in their evolution. METHODS: References were identified through searches of PubMed using the search terms-endoscopy time trends, peptic ulcer disease, gastroesophageal reflux disease, upper gastrointestinal cancer, gastric polyps, H. pylori, eosinophilic gastrointestinal disorders, and celiac disease, from 1970 through December 2021. RESULTS: The prevalence of H. pylori infection has fallen and consequently, H. pylori-positive peptic ulcer disease has become rare. Gastroesophageal reflux disease is now the commonest disorder diagnosed at EGD, and Barrett's esophagus has increased in parallel. Cancer of the distal stomach has fallen while esophageal adenocarcinoma and reflux-related cardia cancer have risen. Gastric polyps have changed from hyperplastic and adenomas to sporadic fundic gland polyps. Antimicrobial resistance has made H. pylori infection more difficult to eradicate. Eosinophilic gastrointestinal disorders, particularly eosinophilic esophagitis, have emerged as important new allergic disorders. Celiac disease has changed and increased. CONCLUSIONS: EGD findings appear to have changed from features suggesting a H. pylori-positive "phenotype" 40 years ago to a H. pylori-negative "phenotype" today. These changes have major implications for the management of gastrointestinal disorders.