Buoyancy-induced mixing occurs during expanded bed adsorption processes when the feed stream entering the bottom of the system has a lower density than that of the fluid above it, such as during the wash step after adsorption of proteins from skim milk. Mixing increases buffer consumption and can be avoided by enhancing the density of the wash buffer with an inert substance such as sucrose or glycerol. The additional cost of the density enhancer can be reduced by initial dilution of the fluid within the system. However, proper economic choice between wash strategies requires a knowledge of the relative buffer volumes involved, as well as raw material and all related operating costs. In this paper, a mathematical model of the mixing dynamics is used to compare buffer volumes for various wash strategies based on initial dilution with wash buffer followed by the use of a density-enhanced wash buffer. The wash strategies were simulated using SuperPro Designer (TM) bioprocess simulation software and the economics were then compared. The results show that the use of density enhancers can reduce raw materials and labor costs but that these can be outweighed in some cases by additional waste treatment costs. The concentration of density enhancer affects not only the degree of density enhancement but also the waste treatment cost. Finally, the results suggest that the use of a short plug of density-enhanced buffer is the optimal approach, if it is feasible, from effectiveness and validation standpoints.