In static SIMS, the secondary ion yield, defined as detected ions per primary ion, can be increased by altering several primary ion parameters. For many years, no quantitative predictions could be made for the secondary ion yield enhancement of molecular ions. For thick samples of organic compounds, a power dependency of the secondary ion yield on the sputtering yield was shown. For this article, samples with thick molecular layers and (sub-)monolayers composed of various molecules were prepared on inorganic substrates such as silicon, silver, and gold, and subsequently analyzed. For primary ion bombardment, monoatomic (Ne+, Ar+, Ga+, Kr+, Xe+, Bi+) as well as polyatomic (Bi-n(+), Bi-n(++)) primary ions were used within an energy range of 10-50 keV. The power dependency was found to hold true for the different samples; however, the exponent decreased with increasing stopping power. Based on these findings, a rule of thumb is proposed for the prediction of the lower limit of the secondary ion yield enhancement as a function of the primary ion species. Additionally, effects caused by the variation of the energy deposition are discussed, including the degree of molecular fragmentation and the non-linear increase of the secondary ion yield when polyatomic primary ions are used. (C) 2012 Elsevier B. V. All rights reserved.