Context: Hepatitis C virus (HCV) has been the main cause of post transfusion hepatitis. Long-term hepatitis can ultimately result in cirrhosis and hepatocellular carcinoma. Viral hepatitis, especially HCV infection, is a major health concern in the Middle East. The current study carried out a systematic search concerning HCV seroprevalence among blood donors in Middle Eastern countries. Evidence Acquisition: Articles were identified through searching databases including PubMed, Scopus, and Web of Science. We reviewed systematically all studies reporting HCV seroprevalence among blood donors in Middle Eastern countries. Results: A total of 5662 relevant records were identified by the electronic search, of which a total of 47 studies were identified as eligible papers that were meta-analyzed for the pooled seroprevalence of HCV among blood donors. Overall, HCV seroprevalence among blood donors in Middle Eastern countries was estimated 0.88% (95%CI = 0.79%-0.97%). The highest pooled HCV seroprevalence rate was related to Egypt (5.76% [95%CI = 3.30%-8.22%]), Libya (1.56% [95%CI = 0.99%-2.13%]), and Yemen (1.09% [95%CI = 0.69%-1.50%]) while the lowest pooled seroprevalence rate was in Iran and Israel with the rates of 0.14% (95%CI = 0.12%-0.17%) and 0.16% (95%CI = 0.06%-0.25%), respectively. Results of annual HCV seroprevalence suggest that there is a decrease in seroprevalence rate of HCV over time among blood donors in Egypt, Iran, Oman, Lebanon, Libya, and Saudi Arabia. Conclusions: Our results showed that the trend of HCV seroprevalence over time among Middle Eastern blood donors was decreasing. It suggests that recent safety measures implemented in Middle Eastern countries have been effective.