We present a systematic study on the synthesis of mixed monolayer-protected clusters (MMPCs) from mixtures of alkanethiols. Our results show that solvation-driven thermodynamic preferential adsorption of precursor ligands governs monolayer composition of MMPCs. In the mixed system HO(CH2)(n)SH/ CH3(CH2)(n)SH (n = m or n not equal m) in toluene, adsorption of the polar component is largely favored because of the poorer solvation of polar tail groups in toluene compared to tetrahydrofuran (THF). When MMPCs are generated from the mixed system HO(CH2)(n)SH/CH3(CH2)(m)SH (n = m) in THF the tail group effect is much less. The MMPC synthesis in THF solutions containing HO(CH2)(n)SH/CH3(CH2)(m)SH (n not equal m) shows large thermodynamic control, which promotes a preferential adsorption of the thiols with a longer alkyl chain onto the surface of clusters. Transmission electron microscopy (TEM) and UV-vis spectroscopy data suggest that the average core dimension of MPCs generated from alkanethiols in THF is slightly smaller than that of MPCs generated from alkanethiols in toluene under the same conditions.