AIM: To investigate the efficacy of combined topical 0.05% cyclosporine A (CsA; Restasis®, Allergan pharmaceuticals, USA) and 0.1% sodium hyaluronate treatment in dry eyes with meibomian gland dysfunction (MGD). METHODS: In a retrospective analysis, 53 patients (106 eyes) with MGD were enrolled and performed lid warm massage for 10min daily and be instilled preservative free sodium hyaluronate 0.1% eye drops 4 times daily. Patients were divided into subjects treated with topical 0.05% CsA and preservative free sodium hyaluronate vehicle (experimental group, n=74 eyes) and subjects treated with the preservative free sodium hyaluronate vehicle (control group, n=32 eyes). They were evaluated at baseline and 1, 2, and 3mo for subjective symptoms and objective signs including tear film break-up time (tBUT), Schirmer test, corneal staining (CS) score, lid margin telangiectasia (LMT), meibomian gland secretion (MGS), and conjunctival injection (CI). RESULTS: In the short-term treatment, the experimental group showed a statistically significant improvement in the ocular surface disease index (OSDI; P<0.001), tBUT (P=0.004), Schirmer test score (P=0.008) and LMT (P=0.021) by repeated measure ANOVA. Additionally, mean changes from baseline in OSDI (P<0.001), tBUT (P=0.001), Schirmer test score (P=0.029), CS score (P=0.047), LMT (P=0.002), CI (P=0.030) were improved better in the experimental group than in the control group at 3mo. However, there was no significant difference between the two groups in MGS (P=0.67). CONCLUSION: In dry eyes with MGD, 0.05% CsA improves the tear film stability as well as subjective ocular discomfort, and is effective in controlling lid margin inflammation.