Gastroesophageal reflux (GER) occurs in 22-66%of patients with noncardiac chest pain (NCCP). Althoughopen-label investigations have shown beneficial effectsof antireflux therapy in NCCP, no double-blind, prospective, placebo-controlled studies havebeen conducted. The purpose of this study was toevaluate the effects of omeprazole compared to placeboin a prospective, double-blind, randomized trial ofpatients with NCCP and GER. Thirty-six consecutivepatients with NCCP and GER documented by 24-hrambulatory pH testing entered this study. The subjectswere randomized to omeprazole, 20 mg by mouth twice aday (17 patients), or placebo (19 patients) foreight weeks. Patients on omeprazole obtainedsignificantly more improvement in the fraction of chestpain days (P = 0.006) and severity (P = 0.032) whencompared to placebo. More patients in the omeprazolegroup reported improvement in individual daily painscores (81% vs 44%, P = 0.03) and individual severityscores (81% vs 50%, P = 0.057). Thirteen (81%) of the subjects in the treatment arm reported overallsymptomatic improvement versus one (6%) in the placebogroup (P = 0.001). The results of this study indicatethat acid suppression with omeprazole effectively improves chest pain in patients with NCCP andGER.