Background and Aim: Acotiamide is a newly developed prokinetic drug that is clinically used to treat functional dyspepsia (FD). The objective of this study was to assess the therapeutic effects of acotiamide in patients with esophageal motility disorders (EMDs). Methods: Twenty-nine patients with both symptoms of FD and symptoms suspicious of EMDs were enrolled. Esophageal motility function was evaluated by high-resolution manometry before and after 2 weeks administration of acotiamide (100 mg) 3 times per day. Results: Twenty-nine patients were diagnosed with achalasia (n = 4), esophagogastric junction outflow obstruction (EGJOO) (n = 6), absent peristalsis (n = 2), distal esophageal spasm (n = 4), frequently failed peristalsis (n = 7), weak peristalsis (n = 2) and 4 of them were found to be normal. An analysis in all 29 patients showed that acotiamide had no effects on based on distal contractile integral (DCI), basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP). Subgroup analysis, however, showed that acotiamide dramatically reduced IRP, from 19.5 (15.1-30.8) to 12.1 (5.6-16.4) mm Hg, and DCI, from 2,517.9 (1,451.0-8,385.0) to 1,872.5 (812.3-5,225.3) mm Hg·cm·s, in the 6 patients with EGJOO. Conclusions: Acotiamide potentially normalized impaired LES relaxation in patients with EGJOO, while having no effects on normal esophageal motility patterns. Acotiamide may be a promising treatment for EGJOO.