The sputtering of bulk organic samples by molecular projectiles is modeled using molecular dynamics simulations. A coarse-grained representation of entangled polyethylene oligomers (1.4 kDa) is used as a model of an amorphous soft material. In this study, a variety of projectiles are compared, including C60, coronene and a series of polystyrene molecular cluster (0.6–110 kDa). The polystyrene clusters bridge the gap between the polyatomic ions (SF5, C60) used in secondary ion mass spectrometry (SIMS) and the large organic microdroplets generated, e.g. in desorption electrospray ionization. In addition, they allow us to explore a wide range of energies/nucleon (0.1–18 eV/nucleon) with projectiles of similar nature and the same total kinetic energy (10 keV). Two regions of sputtering can be distinguished. Above 1 eV/nucleon (smaller projectiles), the sputtering yield depends only on the total projectile energy and not on the projectile nuclearity. Below 1 eV/nucleon (larger projectiles), yields are influenced by both the projectile energy and their nuclearity. Larger projectiles also eject fewer fragments and induce significantly less damage in the sample. A region of intact molecular emission, without induced fragmentation, exists in the < 1 eV/nucleon range. For large clusters, an energy of < 1 eV/nucleon still provides a sputtered mass from the target that is larger than 10 kDa. This region of molecular emission with minimal fragmentation, also attainable with large gas clusters, offers new analytical perspectives. Copyright © 2010 John Wiley & Sons, Ltd.