AIM: To evaluate the efficacy and safety of autologous serum(AS) eye drops with 0.01g/L Thiomersal in the treatment of recalcitrant dry eye syndrome. METHODS: Twenty-six eyes of 13 patients with recalcitrant dry eye syndrome were enrolled in this self-control study, and treated with 2 months of AS 20% with 0.01g/L Thiomersal followed by 2 months of AS 50% with 0.01g/L Thiomersal. Tear membrane lever(TML), tear film break-up time (BUT), corneal fluorescein staining(FL), SchirmerⅠ test with topical anaesthesia(SⅠt), corneal sensitivity test and subjective symptom scoring were performed at entry, 2, 4, 8, 12 and 16 weeks. Statistical analysis was carried out using Wilcoxon''s signed rank test. RESULTS: Both TML and subjective symptom scorning showed significant improvement after 2 weeks of treatment (P<0.01,P<0.05); after 4 weeks of treatment, BUT and FL were significant improvement(P<0.05); SⅠt and corneal sensitivity were significant increased after 8 weeks of treatment(P<0.01,P<0.05). No significant complications were reported in this study. CONCLUSION: AS eye drops 20% with 0.01g/L Thiomersal are effective and safe in treating refractory dry eye syndrome, and should be available as an alternative management option in developing countries.