This paper utilised computational fluid dynamics (CFD) technology to calculate the resistance of a novel high-speed quadramaran in calm water using the Navier‒Stokes (N‒S) equation, analysed the total resistance, frictional resistance, and residual resistance characteristics of this novel high-speed quadramaran at different length Froude numbers, and compared them with the results of a conventional high-speed catamaran with the same displacement. The results showed that the total resistance of the quadramaran had a significant hump at the Froude number of 0.6, due to the complexity of the wave interference among the four demihulls, and the hump value was about 1.6 times that of the catamaran. Above the hump speed, the total resistance of the quadramaran decreased with the increase of the Froude number, until reaching the Froude number of 1.06, when the curve became flat, and it showed a maximum resistance reduction of 40% at the Froude number of 1.66 compared with the catamaran, where the total resistance curve was steep. The frictional resistance of the quadramaran increased gradually with the growth of the Froude number, which was basically consistent with the change trend of the catamaran. The residual resistance of the quadramaran first rose and then reduced with the rising Froude number, the curve showed a large hump due to the adverse wave interference, and the hump value was about 1.7 times that of the catamaran. Above the Froude number of 1.06, as the wave interference changed from adverse to favourable, the quadramaran had lower residual resistance than the catamaran. The bow and stern demihulls of the quadramaran were also analysed for their resistance characteristics. The total resistance of the bow demihulls increased gradually with the increase of the Froude number, the curve had a small hump at the Froude number of 0.7, and above the hump speed, the curve was steep. The total resistance of the stern demihulls first increased and then decreased with the growth of the Froude number, the hump value at the Froude number of 0.85 was significant and was about 2 times that of the bow demihulls, and the curve became flat above the Froude number of 1.51.