Obtaining characteristic molecular information during the secondary ion mass spectrometry (SIMS) depth profiling of polymers has been severely limited due to primary ion-induced sample damage when using monatomic primary ions. Polyatomic primary ions have shown promise for the molecular depth profiling of thin (< 250 nm) polymer films due to their low penetration depth and high sputter rates. In this study, dual-beam time-of-flight SIMS (sputter ion = 5 keV SF@sub 5@@super +@, analysis ion = 10 keV Ar@super +@) was used to depth profile spin-cast multilayers of poly(methyl methacrylate), PMMA, poly(hydroxyethyl methacrylate), PHEMA, and trifluoroacetic anhydride-derivatized PHEMA, TFAA-PHEMA, on silicon substrates. Despite extended SF@sub 5@@super +@ bombardment (> 5 x 10@super 14@ ions/cm@super 2@), characteristic pendant-group-related positive and negative secondary ions of the different polymer layers were observed as a function of depth during the depth profiles. The sputter rates of the polymers in the multilayers typically were lower than corresponding single layer films, with the ion-induced damage accumulation rate of the outermost polymer layer affecting the sputter rate of the underlying layers. Due to its higher ion-induced damage accumulation rate, PHEMA lowered the sputter rates for underlying PMMA or TFAA-PHEMA layers. Similarly, PMMA reduced the sputter rate for underlying TFAA-PHEMA layers. Typical interface widths between adjacent polymer layers were 10-15 nm for the bilayer polymer films; however, the layer order significantly impacted the interface widths for trilayer films. The interface widths in the trilayer films increased with depth to ~ 35 nm, showing the formation of sputter-induced surface roughness during depth profiling of these films. This study demonstrates the utility of polyatomic primary ions for molecular depth profiling and presents new opportunities for the characterization of thin polymer films.