The coarsening resistance and thermal stability of several V plate-dominated microstructures were controlled through altering the chemistry and thermomechanical processing of various Al-Cu-Mg-Ag alloys. Quantitative comparisons of V nucleation density, particle size, and thermal stability were used to illustrate the effects of alloy composition and processing conditions. The long-term stability of V plates was found to coincide with relatively high levels of silver and moderate magnesium additions, with the latter limiting the competition for solute with S-phase precipitation. This analysis revealed that certain microstructures initially dominated by V precipitation were found to remain stable through long-term isothermal and double-aging heat treatments, which represents significant improvement over the previous generation of Al-Cu-Mg-Ag alloys, in which V plates dissolved sacrificially after long aging times. The quantitative precipitate data, in conjunction with a thermodynamic database for the aluminum-rich corner of the Al-Cu-Mg-Ag quaternary system, were used to estimate the chemistry of the a/V-interphase boundary. These calculations suggest that silver is the limiting species at the a/V interfacial layer and that V plates form with varying interfacial chemistries during the early stages of artificial aging, which is directly related to the overall stability of certain plates.