We study how the composition of various surfactant mixtures affects the efficiency of mixed PDMS–silica antifoam in foamed surfactant solutions. First, systematic experiments are performed to characterize the surface and foam film properties of the studied surfactant solutions. The spreading, bridging and entry coefficients are calculated and the spreading ability of the antifoam is characterized by microscopy observations and by surface tension measurements. Next, the initial antifoam activity and the antifoam durability are characterized in foam tests. The obtained results reveal that the antifoam efficiency in solutions of low-molecular mass surfactants with low surface dilatational modulus depends strongly on the density (area-per-molecule) of the respective adsorption layer. The addition of nonionic surfactants, which increase the mean area-per-molecule in the mixed adsorption layer, enhances significantly the antifoam activity and durability. In contrast, the addition of surfactants, which decrease the mean area-per-molecule, suppresses the antifoam activity. Furthermore, we found that surfactant mixtures which form condensed adsorption layers on the solution surface suppress strongly the antifoam activity. As an extreme, the condensed adsorption layer formed from the natural surfactant Quillaja saponin suppresses the antifoam spreading even at highly positive spreading coefficient which results also in very poor AF efficiency. The obtained results rationalize in a coherent way the observed differences in the AF activity and durability in mixed solutions of various ionic, nonionic and zwitterionic surfactants.