Background: Esophagogastric junction outflow obstruction (EGJOO) as defined by Chicago Classification of esophageal motility disorders (CCv3.0) encompasses a broad range of diagnoses, thus posing clinical challenges. Our aims were to evaluate multiple rapid swallow (MRS) and rapid drink challenge (RDC) during high-resolution manometry (HRM) to aid identifying clinically relevant EGJOO. Methods: Patients with a HRM diagnosis of EGJOO based on CCv3.0 that also completed MRS and RDC during HRM and barium esophagram were retrospectively identified. Radiographic EGJOO (RAD-EGJOO) was defined by either liquid barium retention or delayed passage of a barium tablet on barium esophagram. Thirty healthy asymptomatic controls that completed HRM were also included. MRS involved drinking 2 mL for 5 successive swallows. RDC involved rapid drinking of 200 mL liquid. Integrated relaxation pressure (IRP) and presence of panesophageal pressurization (PEP) during MRS and RDC were assessed. Key Results: One hundred one patients, mean (SD) age 56 (16) years, were included; 32% had RAD-EGJOO, 68% did not. RAD-EGJOO patients more frequently had elevated (>12 mmHg) upright IRP (100%), MRS-IRP (56%), RDC-IRP (53%), and PEP during RDC (66%) than both controls [17%; 0%; 7%; 3%] and patients without RAD-EGJOO [83%; 35%; 39%; 41%] Having IRP >12 mmHg during both MRS and RDC was twice as likely to be associated with RAD-EGJOO (19%) than those without RAD-EGJOO (9%) among patients with upright IRP >12 mmHg. Conclusions and Inferences: Adjunctive HRM maneuvers MRS and RDC appear to help identify clinically significant EGJOO. While future outcome studies are needed, comprehensive multimodal evaluation helps clarify relevance of EGJOO on HRM.