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OBJECTIVES: This study aimed to compare temporal changes in tear meniscus height (TMH) and noninvasive tear film break-up time after the instillation of four dry eye treatments: artificial tears (AT), 3% diquafosol sodium long-acting (DQL), 3% diquafosol sodium (DQS), and rebamipide (RB). METHODS: Sixty healthy eyes were randomly divided into four treatment groups. The TMH and noninvasive tear film break-up time were measured using a noninvasive tear film analysis device at baseline and 1, 5, 15, 30, 60, 120, and 180 min after instillation. RESULTS: TMH and noninvasive tear film break-up time did not show significant differences among the groups. In the AT and RB groups, TMH increased significantly 1 min after instillation compared with baseline. In the DQS group, TMH remained elevated for up to 60 min, whereas the DQL group showed a more prolonged increase, lasting up to 120 min. For the noninvasive tear film break-up time, significant prolongation was observed only at 5 and 15 min after instillation in the DQL group. CONCLUSIONS: Topical instillation of 3% diquafosol ophthalmic solution effectively increased tear volume on the ocular surface, with the long-acting DQL formulation demonstrating a more sustained effect in healthy eyes.