Gastroesophageal reflux disease (GERD) accounts for up to 60% of patients with noncardiac chest pain (NCCP). Twenty-four-hour esophageal pH monitoring has been considered the most sensitive test for identifying acid reflux as the probable cause for chest pain. It is unclear if there is a correlation between the degree of esophageal acid exposure as determined by 24-hour esophageal pH monitoring and symptom improvement during a short course of high-dose omeprazole (the omeprazole test) in patients with NCCP due to GERD. Twenty-three patients with GERD-related NCCP were studied. All patients were referred by a cardiologist and evaluated by upper endoscopy and 24-hour esophageal pH monitoring. Diagnosis of GERD was defined by one or both tests being abnormal. Subsequently, patients underwent baseline symptom intensity assessment during 1 week off therapy followed by 1 week on therapy with high-dose omeprazole (40 mg A.M. and 20 mg P.M.). There was a statistically significant correlation between the esophageal acid exposure by 24-hour esophageal pH monitoring and the change in symptom intensity score after treatment. However, there was no significant correlation between the pH values and symptom intensity score during baseline or during the omeprazole test. In patients with GERD-related NCCP undergoing the omeprazole test, 24-hour esophageal pH monitoring has a therapeutic predictive value in addition to its diagnostic merit. Patients with greater esophageal acid exposure appear to have a greater response to antireflux treatment.