AIM: To investigate the ocular surface parameters in patients with moderate to high myopia. METHODS: This prospective study was conducted in May 2023, enrolling patients with moderate to high myopia (spherical equivalent refraction ≤-3.0 D). After completing the Ocular Surface Disease Index (OSDI) questionnaire, refractive parameters and non-invasive tear film parameters were measured, followed by the Schirmer I test and fluorescein sodium staining. The diagnosis of dry eye disease was based on OSDI score, non-invasive tear breakup time (NIBUT), Schirmer I test, and fluorescein sodium staining results, according to the 2020 Chinese Expert Consensus on Dry Eye. The Mann-Whitney U test was used to compare ocular surface parameters between moderate and high myopia, as well as between patients with and without dry eye. Pearson correlation analysis was employed to assess the relationship between the lipid/muco-aqueous layers and tear film parameters. A general linear mixed model (GLMM) was used to analyze the impact of refractive parameters on ocular surface parameters after adjusting for age and sex. RESULTS: A total of 35 eyes with moderate to high myopia (12 males; mean age, 30.30±5.45y) were included in the study. Among them, 26 eyes were classified as normal and 9 as dry eye. Of the 9 dry eye cases, 7 were observed in the high myopia group (n=18) and 2 in the moderate myopia group (n=17). Among the enrolled patients, those with high myopia demonstrated significantly higher OSDI scores than those with moderate myopia (P=0.0417). Patients with dry eye exhibited significantly shorter interblink intervals (P=0.0081) and higher OSDI scores (P=0.0001) than those without dry eye. Pearson correlation analysis revealed a significant positive correlation between lipid layer thickness (LLT) and tear meniscus height (r=0.395, P=0.023), and a significant negative correlation between the muco-aqueous layer thickness change rate (MALTR) and OSDI score (r=-0.466, P=0.016). After adjusting for age and sex using the GLMM, spherical refraction (SPH, β=-1.802, P=0.048) and axial length (AL, β=2.784, P=0.048) significantly impacted OSDI score. Corneal front astigmatism significantly influenced Schirmer I test results (β=8.377, P=0.024). The difference between central corneal thickness and the thinnest corneal thickness significantly affected LLT (β=-2.294, P=0.026). White-to-white diameter significantly impacted MALTR (β=-81.758, P=0.037). CONCLUSION: In moderate to high myopia, higher SPH and AL correlate with increased dry eye symptoms, which are associated with muco-aqueous and lipid layer alterations. Corneal regularity and diameter also affect tear film dynamics.