Objective:To compare the efficacy of autologous serum (AS) eye drops and artificial tears (AT) in dry eye disease (DED).Methods:Five databases (PubMed, Science Direct, the Cochrane Library, the Chinese National Knowledge Infrastructure, and the Wanfang Database) were searched for randomized controlled trials (RCTs). Efficacy was evaluated in terms of the Ocular Surface Disease Index (OSDI), Schirmer I test, tear break-up time (TBUT), and fluorescein and rose bengal staining of ocular surface. The estimated effects of AS or AT were expressed as a proportion with the 95% confidence interval and plotted on a forest plot.Results:Seven RCTs with 267 subjects were included in the meta-analysis. For most of the studies, subjects' age was around 50 years old, and the mostly treatment duration was within 8 weeks. The follow-up results showed that the OSDI after AS treatment was lower than that after the AT treatment: the mean difference (MD) was -10.75 (95% CI, -18.12; -3.39) points. There was no difference on the Schirmer I test after treatment between the two groups: the MD was 1.68 (95% CI, -0.65; 4.00) mm. The TBUT of the AS group was longer than that of the AT group, with an MD of 4.53 (95% CI, 2.02; 7.05) s. There was no statistically significant difference on fluorescein staining score of the ocular surface between the AS group and the AT group, the MD was -2.53 (95% CI, -6.08; 1.03) points. The rose bengal staining score of the AS group was slightly lower than that of the AT group after treatment: the MD was -0.78 (95% CI, -1.34; -0.22) points.Conclusion:AS could be an effective treatment for DED, improving OSDI, TBUT, and rose bengal staining score. Further RCTs with large samples and long-term follow-up are still needed to determine the exact role of AS in the management of DED.