Abstract Time of flight secondary ion mass spectrometry (ToF-SIMS) depth profiles of several inorganic layered samples using Cs + and C 60 + primary sputtering ions of different energies are compared to evaluate sputter yield and depth resolution. A gold/silicon model system is employed to study interfaces between metals and semiconductors, and multilayers of AlGaAs, Al, and InAs in GaAs are analyzed to explore the ability of C 60 + to analyze semiconductor interfaces in GaAs. Roughness measurements are reported to differentiate between different factors affecting depth resolution. The best depth resolution from all samples analyzed is achieved using 1 keV Cs +. However, C 60 + sputtering has advantages for analyzing conductor/insulator interfaces because of its high sputter yield, and for analyzing deeper heterolayers in GaAs due to lower sputter-induced roughness.