Esophagogastric junction outflow obstruction (EGJOO) detected by manometry in the supine position is prevalent in patients with morbid obesity, but not all EGJOOs are clinically significant. We investigated whether including upright swallows during high-resolution manometry (HRM) could help identify non-clinically significant EGJOO in patients with morbid obesity.We performed a retrospective study of consecutive morbidly obese patients diagnosed with EGJOO by HRM from July 2012 through July 2018. The HRM protocol included 10 supine and five upright 5-mL water swallows. Endoscopy, esophagram, and computed tomography were performed to identify whether the patients should be diagnosed as having clinically significant EGJOO.A total of 230 patients with morbid obesity underwent HRM in the supine position during the study period. Fifty (21.7%) patients were diagnosed with EGJOO, among which 32 completed HRM both in the supine and upright positions. Only 8/32 patients were diagnosed with EGJOO in an upright position. Fewer artifacts were displayed in esophageal pressure topography in the upright position. None of the 32 patients could be diagnosed as clinically significant EGJOO based on all the examinations. Median esophageal gastric junction pressure, integrated relaxation pressure, and distal contractile integral were higher, and median distal latency was longer in the supine position compared with the upright position (all P < .05).Esophagus manometry in the upright position could reduce EGJOO overdiagnosis in patients with morbid obesity. Prolongation of the HRM study with some swallows in the upright position could be recommended in obese patients.© 2020 John Wiley & Sons Ltd.