Background: The demand for assessing health-related quality of life (HRQoL) in chronic otitis media (COM) is increasing globally. The currently available Chinese-language patient-reported outcome measurement (PROM) specific for COM includes merely a limited range of related symptoms and dimensions. Hence, in this study, we aim to translate, culturally adapt, and validate the Zurich Chronic Middle Ear Inventory (ZCMEI-21) in Chinese, to enable a comprehensive evaluation of the patients' subjective health outcome in COM. Methods: We sampled and surveyed 223 COM patients at three tertiary referral centers in China, using the Chinese translation of ZCMEI-21 (ZCMEI-21-Chn) and the EQ-5D questionnaire, a generic measure of HRQoL. Confirmatory factor analysis (CFA) was performed to investigate the structural model fit to the dataset. Cronbach's α and test-retest reliability coefficient were calculated to establish reliability, and correlation was tested between ZCMEI-Chn scores and EQ-5D scores for convergent validity. Results: A total of 208 adult patients with COM were included, with a mean age of 46 years (SD 14 years) and a male proportion of 41% (85/208). A modified bifactor model with ωH of 0.65 and ECV of 0.47 was found to fit the scale scores, indicating fair general factor saturation and multidimensionality of the instrument. ZCMEI-21-Chn demonstrated good reliability (Cronbach's α = 0.88, test-retest reliability = 0.88). The total scores of ZCMEI-21-Chn had a moderate correlation with a question directly addressing HRQoL (r = 0.40, p < 0.001), EQ-5D descriptive system score (r = 0.57, p < 0.001), and EQ-5D visual analogous scale (r = 0.30, p < 0.001). Conclusions: The ZCMEI-21-Chn is valid, reliable and culturally adapted to Chinese adult patients with COM. This study offers clinicians an efficient and comprehensive instrument to quantify COM patients' self-reported health outcomes, which could facilitate the standardization of HRQoL data aggregation in COM on a global scale. © 2020 The Author(s).