Two ambient ionisation techniques, desorption electrospray ionisation (DESI) and plasma assisted desorption ionisation (PADI), have been used to analyse personal care products (PCPs) on fixed fibroblast cell surfaces. The similarities and differences between the two techniques for this type of analysis have been explored in various ways. Here, we show the results of DESI and PADI analysis of individual PCP ingredients as well as the analysis of these as complex creams on model skin surfaces, with minimal sample preparation. Typically, organosiloxanes and small molecules were detected from the creams. A study of the morphological damage of the fibroblast cells by the two ionisation techniques showed that for a less than 10% reduction in cell number, acquisition times should be limited to 5 s for PADI, which gives good signal levels; with DESI, the morphological damage was negligible. The operating parameters for the plasma source were optimised, and it was also found that the parameters could be modified to vary the relative intensity of different ions in the mass spectrum.