The OPTN classifies high infectious risk donors (HRDs) based on criteria originally intended to identify people at risk for HIV infection. These donors are sometimes referred to as ‘CDC high risk donors’ in reference to the CDC-published guidelines adopted by the OPTN. However, these guidelines are also being used to identify deceased donors at increased risk of window period (WP) hepatitis C virus (HCV) infection, although not designed for this purpose. The actual risk of WP HCV infection in HRDs is unknown. We performed a systematic review of 3476 abstracts and identified 37 eligible estimates of HCV incidence in HRD populations in the United States/Canada. Pooled HCV incidence was derived and used to estimate the risk of WP infection for each HRD category. Risks ranged from 0.26 to 300.6 per 10 000 donors based on WP for ELISA and 0.027 to 32.4 based on nucleic acid testing (NAT). Injection drug users were at highest risk (32.4 per 10 000 donors by NAT WP), followed by commercial sex workers and donors exhibiting high risk sexual behavior (12.3 per 10 000), men who have sex with men (3.5 per 10 000), incarcerated donors (0.8 per 10 000), donors exposed to HIV infected blood (0.4 per 10 000) and hemophiliacs (0.027 per 10 000). NAT reduced WP risk by approximately 10-fold in each category.