Objective To investigate the effects of non-Newtonian properties on hemodynamic characteristics of Fontan procedure in computational simulation. Methods A Fontan vascular model was reconstructed based on patient-specific medical images. The boundary conditions were set according to velocity profiles measured by real-time echocardiography. The Newtonian model and two non-Newtonian (Casson and Carreau) models were applied to analyze the hemodynamic parameters, including flow ratio (FR), energy loss (EL), wall shear stress (WSS) as well as non-Newtonian importance factor, so as to compare flow differences between the Newtonian model and non-Newtonian models. Results The rheological models had small effects on the FR. The EL of non-Newtonian models was higher than that of the Newtonian model, and the EL of Casson model was the highest. Flow recirculation and flow disturbance accompanied with low WSS were observed in inferior vena cava (IVC). At low inflow velocity, flow disturbance in IVC of Newtonian model was more obvious. The calculations of non-Newtonian importance factor suggested significant non-Newtonian viscosity in IVC. Conclusions Non-Newtonian viscosity is significant in IVC where low velocity and flow recirculation are observed. Non-Newtonian properties of the blood should be considered in patient-specific hemodynamic simulation of Fontan procedure.