Objectives: This study was undertaken to explore which diseases of the ear, nose, and throat impact daily functioning of patients in an outpatient setting and to observe how specific demographic variables affect health-related quality of life (HRQOL) in these patients. Methods: This multicenter observational study was conducted anonymously during a 6-week period at outpatient clinics in adults ≥ 18 years of age. The Short Form-12 (SF-12) was used to assess HRQOL. Demographic and clinical variables were recorded for each patient. Results: In data from 5806 patients, the SF-12 physical component score was 43.8, and the mental component score was 49.4. SF-12 physical and emotional functioning scores for ENT patients were poorer than established standards (50 ± 10) for the U.S. population (P < 0.001). Conclusions: ENT diseases adversely affect the HRQOL in patients visiting their otolaryngologist. Clinical and demographic variables are important considerations in the measurement of HRQOL. (Otolaryngol Head Neck Surg 2001;125:288-98.)