One third of the general population may experience reflux symptoms, yet only a small fraction of patients with gastroesophageal reflux disease (GERD) have Barrett's esophagus. The aim of the present study was to compare the characteristics of GERD patients with and without Barrett's esophagus and identify potential risk factors for the appearance of Barrett's esophagus in reflux disease. Outpatients from a gastroenterology clinic who underwent upper gastrointestinal endoscopy, esophageal manometry, and 24-hr pH monitoring were recruited into a case-control study. A total of 256 case subjects with endoscopically and histologically proven Barrett's esophagus were compared to a control group of 229 subjects with nonerosive reflux disease. As compared to nonerosive reflux disease, Barrett's esophagus was strongly associated with more reflux episodes. Barrett's esophagus occurred more frequently among subjects with hiatus hernia and among subjects who consumed large amounts of alcohol or cigarettes. Frequent reflux episodes, hiatus hernia, smoking, and alcohol consumption were also risk factors for an increased length of Barrett's mucosa. Total esophageal mucosal acid contact time at pH < 4 was a significant risk factor for the length but not the presence of Barrett's esophagus. Intake of aspirin or NSAIDs was similar in patients with and without Barrett's esophagus. In conclusion, in comparison with nonerosive reflux disease, Barrett's esophagus is characterized by risk factors usually indicative of severe types of GERD. Mechanisms in addition to acid reflux must contribute to the development of Barrett's esophagus.