The present paper is concerned with the use of the modified Wöhler curve method (MWCM) to estimate both lifetime and high-cycle fatigue strength of plain engineering materials subjected to complex load histories resulting, at critical locations, in variable amplitude (VA) multiaxial stress states. In more detail, when employed to address the constant amplitude (CA) problem, the MWCM postulates that fatigue damage reaches its maximum value on that material plane (i.e. the so-called critical plane) experiencing the maximum shear stress amplitude, fatigue strength depending on the ratio between the normal and shear stress components relative to the critical plane itself. To extend the use of the above criterion to those situations involving VA loadings, the MWCM is suggested here as being applied by defining the critical plane through that direction experiencing the maximum variance of the resolved shear stress. Such a direction is used also to perform the cycle counting: because the resolved shear stress is a monodimensional quantity, stress cycles are directly counted by the classical rain-flow method. The degree of multiaxiality and non-proportionality of the time-variable stress state at the assumed critical sites instead is suggested as being measured through a suitable stress ratio which accounts for the mean value and the variance of the stress perpendicular to the critical plane as well as for the variance of the shear stress resolved along the direction experiencing the maximum variance of the resolved shear stress. Accuracy and reliability of the proposed approach was checked by using several experimental results taken from the literature. The performed validation exercise seems to strongly support the idea that the approach formalized in the present paper is a powerful engineering tool suitable for estimating fatigue damage under VA multiaxial fatigue loading, and this holds true not only in the medium-cycle, but also in the high-cycle fatigue regime.