This study aimed to evaluate the increase in tear meniscus height (TMH) induced by 3% diquafosol ophthalmic solution in eyes with contact lens (CL).Ten healthy subjects wearing high-water-content CLs received topical instillation of two ophthalmic solutions - 3% diquafosol ophthalmic solution in one eye and artificial tears in the other eye. Lower TMH was measured at 5 minutes, 10 minutes, 15 minutes, 30 minutes, and 60 minutes after instillation by anterior segment optical coherence tomography.TMH increased significantly (P<0.001) at 5 minutes and 15 minutes after instillation of saline compared with the baseline values. After instillation of 3% diquafosol ophthalmic solution, TMH significantly increased (P<0.05) at 5 minutes, 15 minutes, 30 minutes, and 60 minutes compared with the baseline values. Increases in TMH after diquafosol instillation were significantly greater (P<0.05) at 15 minutes, 30 minutes, and 60 minutes than increases in TMH after saline instillation.Topical instillation of 3% diquafosol ophthalmic solution increases TMH for up to 60 minutes in eyes with high-water-content CLs.