© 2021 Taylor & Francis.Purpose: To investigate the impact of long-term scleral contact lens (ScCL) wear on corneal curvature, corneal thickness, tear film function, and ocular surface in patients with keratoconus.Methods: Sixteen keratoconus patients wearing ScCLs for 6 months were enrolled in the study. Corneal topography, tear osmolarity test, Schirmer 1 test, tear film break-up time (TBUT) test, and impression cytology analysis were assessed at baseline and follow-up examinations.Results: There were no significant differences in visual acuity, keratometric and pachymetric values after 6 months of ScCL wear compared to baseline (p>0.05 for all). Tear osmolarity, Schirmer 1 test, and TBUT test results showed no significant change during follow-up (p>0.05 for all). Median goblet cell density and grade of squamous metaplasia did not differ significantly at 1-month. However, there was a gradual deterioration in goblet cell density and Nelson grade until the third-month visit compared to baseline (p for goblet cell, p=0.003; p for Nelson grade, p=0.003). These impaired cytological features observed at 3-month visit persisted at 6-month visit (p for goblet cell, p=0.008; p for Nelson grade, p<0.001).Conclusion: Six months of ScCL wear did not induce any changes in corneal curvature and thickness and also did not affect tear function tests in keratoconic eyes. The only significant changes observed were a decrease in goblet cell density and metaplastic changes in conjunctival epithelium in impression cytology analysis. Further investigations may be needed to better understand the cause of impairment in cytological features of ocular surface and its clinical implications.