Transiently elevating pressure in a matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) source into the 1-10 mbar range during ionization decreases the metastable fragmentation of gangliosides. This allows detection of the molecular ion species without loss of the highly labile sialic acid residues. In these experiments, gangliosides with up to five sialic acids were ionized by MALDI and detected with the FTMS. In each case, when the high pressure collisional cooling was used, the singly charged molecular ion was the base peak in the spectra, both in the positive and negative ion modes, and minimal metastable fragmentation was observed. This result is promising, as the previously developed TLC separation methods can be coupled to MALDI-FTMS.