Background/Aims: To evaluate the effects of topical cyclosporin A (CsA) and artificial tears (ATs) for treating patients with dry-eye disease (DED). Methods: On January 25, 2019, five electronic databases and reference lists were searched for randomized clinical trials (RCTs) comparing CsA with ATs among patients with DED. The search strategy had no restriction on language or time. Two authors extracted surgery, mean age, anesthesia for Schirmer's test, tear-breakup time, Schirmer's test score, fluorescein-staining score, ocular surface-disease index, and adverse events. Mean differences (MDs) were calculated for continuous outcomes and Peto ORs for dichotomous data with zero cells. Results were analyzed with 95% CIs in a random-effect model. Results: Eleven RCTs recruiting 1,085 cases with DED were included. Pooled results showed that CsA had better tear-breakup time (MD 0.94, 95% CI 0.08-1.80), fluoresceinstaining score (standardized MD −0.72, 95% CI −1.28 to −0.16), and ocular surface-disease index (MD −4.75, 95% CI −6.31 to −3.18) when compared to ATs. Although CsA had more adverse events than ATs (Peto OR 7.70, 95% CI 3.17-18.68), no serious adverse events were reported. Conclusion: Overall, CsA is an effective option for treating patients with DED, yet our evidence indicated decreasing effects when CsA was combined with ATs. CsA may be worth suggesting to relatively older patients with DED. We anticipate further RCTs to explore the effects of treatment duration, optimal dosage, and efficacy of CsA in different DED etiology.