We conclude that with the "OrthoBoXY" approach of employing orthorhombic systems with "magic" box length ratios of L z /L x = L z /L y ≈ 2.7933596497, we are consistently able to determine the true (i.e. system size independent) self-diffusion coefficients D 0 and viscosities η for a variety of different systems from a single MD simulation run. To show this, we have studied a multitude of systems: liquid water, dimethyl ether, methanol, triglyme, water/methanol mixtures, water/triglyme mixtures, and imidazolium-based ionic liquids. The chosen systems range from small-sized molecular liquids to complex mixtures and ionic liquids, while spanning a viscosity range of almost three orders of magnitude. Based on results of simulations of liquid TIP4P/2005 water, we have devised a strategy for how to set up the simulation runs to obtain both D 0 and η with a targeted accuracy, while taking into account both the molecule size and mobility. Our analysis of the system size dependence of statistical uncertainties for both the viscosity and the self-diffusion coefficient leads us to the conclusion that it is preferable to extend the simulation length instead of increasing the system size. Moreover, since the statistical uncertainty of the computed viscosity is found to be system size independent, it is most economical to focus on small systems sizes. We have no evidence to believe that a system size of 768 molecules or ion pairs is not sufficient for this purpose.