Clinical reports suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) use might induce esophageal symptoms and damage, including esophagitis, but experimental data are conflicting, and some indicate that NSAIDs improve mucosal damage. It is not known whether patients with endoscopically diagnosed esophagitis during NSAID use have different baseline reflux patterns from patients with reflux esophagitis and no NSAID use. Two groups of patients with and without chronic NSAID use and esophagitis were prospectively studied. Twenty-four-hour pH monitoring and esophageal manometry were performed in all patients who were free of NSAID and any other drug use during tests. Esophageal motility and reflux patterns did not differ in patients with esophagitis regardless of the presence or absence of NSAID use. However, the subgroup of patients with grades II and III esophagitis and chronic NSAID use had a significantly greater lower esophageal sphincter (LES) pressure and a less severe intraesophageal pH profile than patients without NSAID use. In agreement with clinical reports, these results suggest that NSAID use may aggravate an otherwise milder acid-related esophageal disease in a subgroup of patients.