New guidelines and suggestions for taking reliable effective relative permeability measurements in heterogeneous rocks are presented. The results are based on a combination of high resolution of 3D core-flooding simulations and semi-analytical solutions for the heterogeneous cores. Synthetic “data sets” are generated using TOUGH2 and are subsequently used to calculate effective relative permeability curves. A comparison between the input relative permeability curves and “calculated” relative permeability is used to assess the accuracy of the “measured” values. The results show that, for a capillary number (Ncv = kLpc × A/H2μCO2qt) smaller than a critical value, flows are viscous dominated. Under these conditions, saturation depends only on the fractional flow as well as capillary heterogeneity, and is independent of flow rate, gravity, permeability, core length, and interfacial tension. Accurate whole-core effective relative permeability measurements can be obtained regardless of the orientation of the core and for a high degree of heterogeneity under a range of relevant and practical conditions. Importantly, the transition from the viscous to gravity/capillary dominated flow regimes occurs at much higher flow rates for heterogeneous rocks. For the capillary numbers larger than the critical value, saturation gradients develop along the length of the core and accurate relative permeability measurements are not obtained using traditional steady-state methods. However, if capillary pressure measurements at the end of the core are available or can be estimated from independently measured capillary pressure curves and the measured saturation at the inlet and outlet of the core, accurate effective relative permeability measurements can be obtained even when there is a small saturation gradient across the core.