Abstract Carbon dioxide (CO2) is becoming an important commercial and industrial working fluid as a potential replacement of the non-environmental friendly refrigerants. For refrigeration and power systems, the minichannel heat exchangers are becoming attractive for transcritical CO2 Rankine cycle and supercritical CO2 Brayton cycle, due to their highly compact construction, high heat transfer coefficient, high pressure capability and lower fluid inventory. This paper employs three-dimensional numerical models to investigate the heat transfer and pressure drop characteristics of supercritical CO2 in minichannels. The models consider real gas thermophysical properties and buoyancy effect and investigate the effect of cross-section geometry on the thermohydraulic characteristics. Six minichannel cross-section geometries with the same hydraulic diameter of 1.22 mm are considered. The geometries include circle, semicircle, square, equilateral triangle, rectangle (aspect ratio = 2) and ellipse (aspect ratio = 2). The inlet temperature, outlet pressure and wall heat flux are 35 °C/75 bar/100 kW/m2 and 35 °C/150 bar/300 kW/m2 for heating conditions and 120 °C/75 bar/-100 kW/m2 and 120 °C/150 bar/-300 kW/m2 for cooling conditions. Comparisons of local Nusselt number and friction factor with those employed empirical correlations are made and useful information and guidelines are provided for the design of compact heat exchangers for supercritical CO2 power system applications.