OBJECTIVEHuman endogenous retroviruses (HERV) are the remnants of infections that occurred million years ago. They gradually integrated into the human genome, comprising 8 % of it. There are growing reports suggesting their potential role in various diseases, including schizophrenia. Schizophrenia, a serious psychiatric disorder, is caused by the interaction of genetic and environmental factors. In the present paper, we investigated studies focusing on the association between schizophrenia and HERV-W.METHODSWe registered this study at PROSPERO (registration number: CRD42022301122). The entire steps of this study were based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. We searched PubMed, Scopus, Web of Science, and Google Scholar up to 1 August 2022. Heterogeneity was estimated through I2 statistics, and the association was measured using the first estimate and penalization methods.RESULTSFinally, 13 eligible studies were analyzed, including 698 cases and 728 controls. The overall odds ratio indicated a significant association in both the first estimate (OR = 9.34, 95 % CI = 4.92-17.75; P = 0.002) and penalization (OR = 7.38, 95 % CI = 4.15-13.10; P = 0.003) methods. In the subgroup analysis, among HERV-W fragments, the HERV-W envelope protein or RNA (OR = 11.41, 95 % CI: 5.67-22.97; P = 0.03) showed the strongest association with schizophrenia.CONCLUSIONOur meta-analysis showed that HERV-W is significantly associated with schizophrenia. More studies are required to determine the pathophysiological mechanism and the diagnostic, prognostic, and therapeutic value of HERV-W in schizophrenia.