Objective To assess the efficacy and safety of esomeprazole in long-term or intermittent treatment of gastroesophageal reflux disease (GERD). Methods Twenty-eight patients with GERD who accepted esomeprazole 20 mg bid for 2 weeks were further divided into long-term treatment group and intermittent treatment group according to the protocol of therapy. Patients in long-term treatment group were received minimum dose that was needed to relief the symptoms for more than 6 months, whereas those in intermittent treatment group were received esomeprazole 20 mg qd until the symptoms completely disappeared, if symptoms relapsed the patients were treated again.The dosage, recurrence of symptoms and the side effects were compared between two groups. ResultsThirteen patients in long-term treatment group were treated for 7-44 months (20 mg daily in 7,twice daily in 5 and every other day in 1). While 15 patients in intermittent treatment group had a good relief of the symptoms. No adverse reactions was found in two groups. The follow-up study of 10-57 months in intermittent treatment group revcaled that the longer the treatment maintained,the longer the symptoms relieved (r=0. 447, P= 0. 008). Conclusion It is safe for esomeprazole in relieving symptoms of patients with GERD by long time or intermittent use.