Purpose Primary objective of this study was to identify potential difficulties and/or discomfort when using a facemask. Moreover, to explore the impact of spectacles, contact lenses and visual acuity on the compliance to the facemask directive. Methods This is a prospective study that was conducted at the Department of Ophthalmology, University Hospital of Alexandroupolis, Greece between June 2020 and August 2020. Greek speaking citizens with permanent residency in Greece above 18 years old were included. A custom questionnaire (DeMask-20) was constructed and validated, which pertained to the perceived difficulty and discomfort when using a facemask. It contained 20 items grouped in 8 subscales (driving, near vision, distance vision, ocular discomfort, role limitation, collaboration, dependency on others, emotional stress). Perceived difficulty and discomfort when using a facemask, compliance and correlations of compliance with DeMask-20 scores, demographics, spectacle and/or contact lens use, and visual acuity were evaluated. Results The number of factors was determined through factor analysis. Cronbach's alpha ranged from 0.716 for the "Role limitation" subscale to 0.938 for "Ocular discomfort" subscale. 1,214 participants (402 men, 812 women, mean age 36.79±12.50 years) completed the DeMask-20 instrument. Mean DeMask-20 score of all study participants was 3.79±0.71. Significant differences in DeMask-20 score were detected in gender (p = 0.009), spectacle use (p = 0.034), contact lens use (p = 0.049), and binocular distance visual acuity (bDVA) (p = 0.001). Mean compliance of all participants was 4.05±0.96. Men, people Conclusions Factor analysis suggested that the DeMask-20 instrument demonstrates adequate validity, while Cronbach's alpha indicated sufficient internal consistency of all subscales. This study provided the necessary methods that could evaluate compliance trends and the efficacy of healthcare interventions against COVID-19. Our outcomes suggest that young males who use spectacles should be targeted by Greek Healthcare authorities in order to improve compliance rates.