Matrix-enhanced surface-assisted laser desorption ionization mass spectrometry imaging (ME-SALDI MSI) has been previously demonstrated as a viable approach to improving MS imaging sensitivity. We describe here the employment of ionic matrices to replace conventional MALDI matrices as the coating layer with the aims of reducing analyte redistribution during sample preparation and improving matrix vacuum stability during imaging. In this study, CHCA/ANI (alpha-cyano-4-hydroxycinnamic acid/aniline) was deposited atop tissue samples through sublimation to eliminate redistribution of analytes of interest on the tissue surface. The resulting film was visually homogeneous under an optical microscope. Excellent vacuum stability of the ionic matrix was quantitatively compared with the conventional matrix. The subsequently improved ionization efficiency of the analytes over traditional MALDI was demonstrated. The benefits of using the ionic matrix in MS imaging were apparent in the analysis of garlic tissue sections in the ME-SALDI MSI mode.