Background: Empty nose syndrome (ENS) is considered an acquired condition that remains difficult to diagnose objectively. Defining specific symptoms that can be reliably associated with this disorder would be essential to identifying possible ENS patients. We sought to validate an ENS-specific, 6-item questionnaire as an adjunct to the standard Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire to discriminate patients suspected of having ENS. Methods: The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) paired 6 common ENS symptoms (nasal suffocation, nasal burning, nasal openness, crusting, dryness, and impaired air sensation through nasal cavities) with testing on 75 patients divided in 3 patient cohorts: ENS; chronic rhinosinusitis without polyposis; and healthy controls. Participants answered 2 rounds of both the SNOT-22 questionnaire and ENS6Q within 48 hours of each other. No changes in treatments occurred in the test interval between questionnaires. Internal consistency, test-retest reliability, validity, and area under the curve were assessed to differentiate between patient cohorts using the 2 instruments. Results: We found high internal consistency for ENS6Q and SNOT-22 questionnaire at 0.93 (95% CI, 0.900.95) and 0.94 (95% CI, 0.94-0.96), respectively. The test-retest reliability between timepoints for ENS6Q testing was 0.969. The ENS6Q statistically significantly discriminated between ENS and control patients and between ENS and chronic rhinosinusitis without polyposis (CRSsNP) patients, without significant differences between CRSsNP and controls. The area-under-the-curve (AUC) threshold score comparison further supported the ability of the ENS6Q to differentiate ENS from CRSsNP patients. Conclusion: The ENS6Q is the first validated, specific, adjunct questionnaire to the SNOT-22 to more reliably identify patients suspected of developing ENS. (C) 2016 ARS-AAOA, LLC.