Purpose: The goals of this study were to compare the efficacy and safety profile of topical cyclosporine 0.05% versus vehicle in Chinese patients with moderate to severe dry eye disease. Methods: In this multicenter, randomized, double-blind, vehicle-controlled, parallel-group study, 233 dry eye patients were allocated to receive either cyclosporine 0.05% or vehicle twice daily for 8 weeks. Primary outcome was the difference between groups, in total score of 4 symptoms and 4 signs change from baseline at weeks 2, 4, and 8. Changes in symptoms (ocular dryness, foreign body sensation, photophobia and burning) and signs (conjunctival hyperemia, Schirmer test, tear Break-up time (BUT), and corneal punctate fluorescein staining) at weeks 2, 4, and 8 as well as frequency of administration of concomitant artificial tears, were considered as secondary outcomes. The safety profile was evaluated by examining adverse events, changes in visual acuity, and ocular tolerance. Results: Greater improvements of the total score were seen in cyclosporine 0.05% group than in the vehicle group at all follow-up times (P<0.01). Improvements in ocular dryness at week 8 (P=0.040) and foreign body sensation during weeks 4 and 8 (P<0.020) were significantly greater with cyclosporine. In addition, compared with the vehicle, cyclosporine significantly improved 2 objective dry eye disease signs: corneal staining at weeks 4 (P=0.025) and 8 (P=0.050) and the Schirmer test at week 4 (P=0.035). However, no between-group difference approached statistical significance in photophobia, burning, BUT value, conjunctival hyperemia and frequency of administration of concomitant artificial tears at any follow-up times (P>0.05). The cumulative frequency of adverse events did not significantly differ between the groups (P=0.519), which were 11.21% and 8.55%, respectively. There were no patients who experienced reduced visual acuity. Conclusion: Cyclosporine 0.05% ophthalmic emulsion is an effective and safe treatment for Chinese patients with moderate to severe dry eye disease.