OBJECTIVES Chronic infection with hepatitis C virus (HCV) is a major public health concern in Egypt. Prevalence data exist, but methods to estimate the epidemiologic burden have varied and there has been no systematic approach to synthesize these data. The objective of this study is to synthesize published reports of prevalence and estimate the total number of HCV cases in Egypt. METHODS A systematic search was implemented by two reviewers in the EMBASE, Medline, and Cochrane databases, to identify and extract data from population-based studies of the epidemiologic burden of HCV in Egypt. Estimates based on laboratory-confirmed HCV infection, published between January 1, 1995 and May 13, 2014, were included. Published data were supplemented with data from the National Blood Transfusion Center (NBTC) in Egypt. 2014 population estimates were used to project the number of persons infected based on synthesized prevalence estimates. RESULTS From 630 abstracts, 23 studies were identified. The population-based Demographic and Health Survey (DHS) estimated the prevalence of active infection at 9.8% and overall HCV infection at 14.9%; which is likely an underestimate of e the total population affected since DHS was restricted to people 15 to 55 years of age. Estimates from blood donors from the NBTC were ~7.5%, supporting the low estimate from DHS. Population-based estimates from studies conducted in areas of high infectivity were as high as 40 to 50% HCV prevalence. Based on a prevalence estimate of 15% (12-18%), approximately 13 million (10-16 million) people are infected with HCV in Egypt. CONCLUSIONS Although estimates of the prevalence of HCV vary, the wealth of evidence suggests that there is an extensive epidemiologic burden in Egypt. With the availability of new therapies, decision-makers and clinicians need accurate estimate of disease prevalence to assess the cost-benefit ratio of new HCV treatments.