PurposeNasoseptal perforations (NSP) are a clinically heterogeneous group of disorders with a wide range of available treatments. Patient-reported outcome measures (PROMs) can provide valuable insights for assessing clinical and surgical outcomes. This study aims to develop and validate a novel-specific questionnaire for patients with NSP.MethodsA multi-centre prospective observational study was conducted at two tertiary referral hospitals. “Septal Perforation Quality of Life” (SEPEQOL) was developed by a committee of experts. The psychometric properties, including reproducibility, reliability, validity, and responsiveness, were assessed.ResultsThe study included 96 symptomatic NSP patients and 30 healthy controls. SEPEQOL internal consistency was satisfactory [Cronbach´s α = 0.7843; 95% confidence interval (CI), 0.702–0.856]. Test-retest reliability was excellent, demonstrated by the absolute intraclass correlation (ICC = 0.974; 95% CI, 0.935–0.989, P-value < 0.001) and Bland-Altman plot (line bias = 1.6 ± 4.57; 95% CI -0.54–3.74, P-value < 0.001). The mean total SEPEQOL score was higher before surgery (25.16 ± 1.65) compared to 6-months after the procedure (13.72 ± 11.39), with a mean difference of 12.19 [standard deviation (SD) 10.76], P-value < 0.001.ConclusionsSEPEQOL is reliable, consistent, valid, and sensitive to change over time. SEPEQOL assesses the impact of health-related quality of life on NSP and its management in clinical practice. Moreover, it is easy to apply in clinical settings with minimal burden.