The aim of this paper was to illustrate the value of the new metric effective detective quantum efficiency (eDQE) in relation to more established measures in the optimization process of two mammography systems. The following metrics were included for comparison against eDQE: detective quantum efficiency (DQE), signal difference to noise ratio (SdNR), and detectability index (d’) calculated using a standard nonprewhitened observer with eye filter. The systems investigated were the Siemens Inspiration and the Hologic Selenia. The eDQE, SdNR, and d’ were measured for four poly(methyl methacrylate) (PMMA) thicknesses, with and without antiscatter grid and for all clinically relevant target/filter (T/F) combinations. Figures of merit were then formed from SdNR and d’ using the mean glandular dose as the factor to express detriment. DQE was measured at energies covering the range of typical clinically used spectra. Both DQE and eDQE data showed only a small sensitivity to T/F setting for these systems. The eDQE showed clear preferences in terms of scatter reduction, being highest for the grid-in geometry for PMMA thicknesses of 40 mm and above. The SdNR and d’ based figures of merit, which contain additional weighting for contrast and dose, pointed to specific T/F settings for both systems.