Background: The 22-item Sino-Nasal Outcome Test (SNOT-22) is a widely used questionnaire to measure disease-specific health-related quality of life in patients with chronic rhinosinusitis (CRS). The Dutch version has not been validated yet. Methods: The SNOT-22 was translated through a forward-backward translation technique and validated by a test-retest protocol in CRS patients, a responsiveness analysis in CRS patients treated with dupilumab, while using healthy individuals as controls. Results: The Dutch SNOT-22 showed excellent test-retest properties, good responsiveness to treatment with dupilumab, and a clear distinction between outcomes of CRS patients and healthy controls. Conclusion: The Dutch version of the SNOT-22 is a valid outcome measure in CRS patients.