Idiopathic achalasia (IA) is a primary motor disorder of the esophagus. Recently, ethanolamine oleate (EO) has been introduced as a novel therapy in IA. We investigate the long-term efficacy of EO injection in the selected IA patients. Two hundred twenty patients with IA were evaluated prospectively. Thirty-one patients who were resistant to or poor candidate of pneumatic balloon dilation and/or cardiomyotomy were enrolled in this study. EO was injected into the lower esophageal sphincter three times at 2-week intervals. Patients were evaluated with the achalasia symptom score (ASS), timed barium esophagogram, and manometry before and after the injections. A good response was defined as a greater than 50% reduction from baseline in the ASS, height and/or volume of barium in TBE, and absence of severe dysphagia or regurgitation at 1.5 months after the last injection. Relapse was defined as two or more points increase in dysphagia score after an initial good response. The mean age of patients was 49.32 ± 19.3 years. Twenty-nine patients had a good response and two had a poor response. The mean ASS decreased from 12.48 (±2.06) to 4.50 (±2.96) (P = 0.0001), and the mean volume of barium decreased from 115.35 (±93.40) to 45.50 (±60.86) mL at 1.5 months after the last injection (P = 0.0001).The mean lower esophageal sphincter pressure was 30.47 ± 13.95 before the treatment and decreased to 14.30 ± 11.89 at 1.5 months after the treatment. (P = 0.0001). The mean duration of follow up was 30.16 ± 11.3 (18-68) months. Twelve patients in whom symptoms relapsed were treated effectively with reinjection. In some patients, minor complications (chest pain and erosion in the distal esophagus) occurred. This study indicates that EO has a long-term effect and can be considered for use in the selected IA patients.