The JMS-S3000 SpiralTOF TM is a time-of-flight mass spectrometer (TOFMS) employing matrix-assisted laser desorption ionization (MALDI). MALDI is a soft ionization technique that generally keeps the ions intact during ionization. However, spontaneous fragmentation after ionization, called post-source decay (PSD), is also well known to occur during MALDI analysis. In particular, as the analyte molecular weight increases, the PSD effect becomes more pronounced which complicates the resulting mass spectra and reduces the overall analyte signals. The SpiralTOF has a 17m folded ion optical path that automatically decreases the amount of PSD ions reaching the detector, thus minimizing the complexity of the mass spectra. Additionally, choosing an appropriate matrix can decrease PSD, which in turn can improve the intact protein signal. In this study, we used the JMS-S3000 to test several matrices for PSD effects and to measure high resolution mass spectra of intact insulin, ubiquitin and cytochrome C.