Chronic HDV infection often is associated with aggressive form of liver disease, compared to chronic HBV mono-infection. However, chronic HDV treatment is challenging because currently there is no approved regimen for affected patients. While standard interferon with/without nucleos(t)ide analogues were reported to be inferior to pegylated interferon (peginterferon) as HDV treatment according to few randomized clinical trials. This meta-analysis will summarize the results of studies on the effectiveness of peginterferon as HDV treatment regimen. An electronic search was performed using PubMed, Cochrane Library, Research Gate, and Medline databases. Studies involving patients who received peginterferon therapy for at least 48 weeks and followed up for 24 weeks post-therapy were included. All analyses were conducted using Review Manager 5.3 designed for Cochrane Reviews. The primary efficacy endpoint was virological response (VR) or HDV-RNA negativity at the end of the follow-up period, whereas secondary efficacy endpoints were biochemical response (BR) or ALT normalization and HBsAg clearance with seroconversion to anti-HBs at the end of follow-up period. Data were abstracted from 13 relevant studies with a total of 475 patients who were treated with peginterferon alpha-2a or -2b. At the end of 24-week post-treatment the pooled VR was achieved in 29% of patients with 95% CI [24%;34%], BR was reached in 33% of patients [95% CI 27%;40%] and HBsAg clearance with seroconversion to anti-HBs was achieved in 1% of patients with 95% CI [-0.02;0.05]. In conclusion, this study showed that peginterferon has limited effectiveness in HDV treatment, since only one-third of chronic HDV patients achieved viral clearance and normalized ALT levels. Morever, HBsAg clearance with seroconversion to anti-HBs has been rarely observed among chronic HDV patients.Copyright © 2020. Published by Elsevier B.V.