The centrifugal turbine architecture is a promising solution for small-to-medium organic Rankine cycle (ORC) power systems. The inherent compactness of the multistage arrangement makes this configuration very attractive for dealing with the high volumetric flow ratios typical of ORC turbines. In absence of experimental evidence, a thorough assessment of the technology can be uniquely based on sufficiently accurate computational fluid dynamic (CFD) simulations. In the present work, the aerodynamic performance of a fixed and a rotating cascade of centrifugal turbine are investigated by applying a three-dimensional CFD model. Precisely, the study is focused on the sixth stage of the transonic centrifugal turbine proposed in Pini et al. (2013, “Preliminary Design of a Centrifugal Turbine for ORC Applications,” ASME J. Eng. Gas Turbines Power, 135(4), p. 042312). After recalling the blade design methodology, the blade-to-blade and secondary flow patterns are carefully studied for both stator and rotor. Results show that the centrifugal configuration exhibits distinctive features if compared to axial turbine layouts. The diverging shape of the bladed channel and the centrifugal force alter significantly the pressure distribution on the profile. Moreover, the Coriolis force induces a slip effect that should be properly included in the preliminary design phase. Provided that the flaring angle is limited, the almost uniform spanwise blade loading greatly augments the three-dimensional performance of the cascades compared to axial rows. In the rotor, the low inlet endwall vorticity and the Coriolis force further weaken the secondary flows, resulting in even lower secondary losses with respect to those predicted by loss models developed for axial turbines. Ultimately, the efficiency of the stage is found to be two points higher than that estimated at preliminary design level, demonstrating the high potential of the centrifugal turbine for ORC applications.