PURPOSE: To evaluate the effects of topical 0.05% cyclospo- rine A on Ocular Surface Disease Index (OSDI) score and ocu- lar surface parameters after small incision lenticule extrac- tion (SMILE) for myopia. METHODS: In this study, 151 patients who underwent SMILE were randomized into the control group (71 eyes) and the 0.05% cyclosporine A group (80 eyes). Both groups received standard treatment during the 1 month after SMILE. Over the next 3 months, The control group continued standard therapy (0.3% sodium hyaluronate) and the 0.05% cyclosporine A group received additional 0.05% cyclosporine A. OSDI total and subscale scores, non -invasive tear break -up time (NIBUT), tear lipid layer thickness (LLT), and tear meniscus height (TMH) were assessed preoperatively and postoperatively. RESULTS: Compared to baseline, the OSDI scores significantly increased in both groups (P < .001). The 0.05% cyclosporine A group exhibited lower OSDI total scores after administering 0.05% cyclosporine A versus the control group (P = .026). At 1 month of follow-up, NIBUT, LLT, and TMH values significantly decreased in both groups compared to baseline (P < .05). The 0.05% cyclosporine A group exhibited higher NIBUT, LLT, and TMH versus the control group, returning to preoperative val- ues after 2 months. Overall, the OSDI total score and NIBUT values during follow-up were not significantly different be- tween the two groups; however, the LLT and TMH values were significantly different between the two groups (P < .001 and .041, respectively) by repeated measures analysis of variance. CONCLUSIONS: Topical 0.05% cyclosporine A was effective in relieving subjective dry eye symptoms and maintaining ocular surface stability in the early postoperative period of SMILE. [J Refract Surg. 2024;40(4):e229 -e238.]