Fenestration has been reported to enhance Fontan hemodynamics in several cases of Fontan circulation. However, the indication criteria for fenestration remain under discussion. To assess the effectiveness of fenestration in Fontan circulation, we conducted a theoretical analysis using a computational model of the fenestrated Fontan circulation. The cardiac chambers and vascular systems were modeled using the time-varying elastance model and the modified Windkessel model, respectively. When the pulmonary vascular resistance index was 4.01 Wood units m2, fenestration significantly reduced central venous pressure from 18.0 to 16.1 mmHg and decreased stressed blood volume from 610 to 555 ml. However, in the models with reduced ventricular end-systolic elastance, increased ventricular stiffness constant, or heightened systemic vascular resistance, the advantages of fenestration were diminished. Thus, fenestration may effectively improve the hemodynamics of Fontan circulation in patients with elevated pulmonary vascular resistance.