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We investigated the 5-year clinical course in a cohort of patients with typical reflux symptoms and negative endoscopy. Prospective follow-up was conducted in patients with non-erosive reflux disease (NERD) for at least 5 years after initial evaluation with esophageal pH monitoring and upper gastrointestinal endoscopy. Within the last year of follow-up, reflux symptoms occurred in 27 of the 30 patients (90%). Twenty-five of twenty-seven symptomatic patients (93%) were on acid suppression therapy. The majority of our patients (70%) remained unchanged regarding their endoscopic status over 5 years. Progression to erosive esophagitis occurred in four patients with Los Angeles (LA) A (13%), three patients with LA B (10%), and two patients with LA C (7%). The presence of pathological acid exposure did not alter the presence of reflux symptoms over 5 years. Disease progression to erosive esophagitis occurred more frequently in patients with pathological acid exposure than those without pathological acid exposure ( P= 0.025). Most NERD patients have symptoms and require acid suppression therapy 5 years after their initial diagnosis. Initial pathological acid exposure does not influence the use of acid suppression; however, it does influence the progression of NERD within 5 years of follow-up. [ABSTRACT FROM AUTHOR]