This study describes the reliability, validity, and responsiveness of the Sinonasal Outcome Test-16 (SNOT-16), a rhinosinusitis-specific health-related quality-of-life instrument, in the University of Washington Department of Otolaryngology-Head and Neck Surgery patient population. The SNOT-16 was completed by 47, 24, and 22 patients at weeks 0, 6, and 12, respectively. In addition, all 47 patients completed the Short-form 36-item Health Survey (SF-36) at week 0. Furthermore, an additional cohort of patients from the otology clinic who denied symptoms of rhinosinusitis or previous physician diagnoses of rhinosinusitis were asked to complete the SNOT-16. These scores were subsequently used to determine discriminant validity of the instrument. Cronbach's alpha was 0.89, indicating a high degree of homogeneity of the test items. The SNOT-16 demonstrated excellent discriminant validity, and mean total SNOT-16 scores were significantly correlated with patient-reported overall health, overall bother, and 7 of the 8 SF-36 subscales. The standardized response mean calculated between weeks 0 and 6 was 0.69, indicating moderate sensitivity to change. We conclude that the SNOT-16 is a reliable, valid, and responsive instrument for measuring rhinosinusitis-specific health-related quality of life.