Mass spectrometry has played a key role in identifying the members of a series of gold clusters, which has enabled the development of magic-number cluster theory. The successes of the gold cluster system have yet to be repeated in another metal cluster system, however. Silver clusters in particular have proven to be challenging due to their relative instability compared with gold clusters. Using the well-characterized gold nanocluster, Au 25(SG) 18, we present optimized electrospray ionization mass spectrometry (ESI-MS) instrumental parameters for the maximal transmission of the intact cluster. Parameters shown to have the largest effect on intact cluster transmission/detection include trap and transfer collision energy, source temperature, and cone gas flow rate. Herein we describe a general strategy to acquire mass spectra of fragile metal clusters with reliable mass assignments. By also optimizing sample solution conditions, high-quality ESI mass spectra of a prototypical silver:glutathione (Ag:SG) cluster were obtained without significant fragmentation. By using gentle conditions and solution conditions designed to stabilize the clusters, fragmentation was dramatically reduced and mass spectra with isotopic resolution were measured. Using this strategy, we have made the first formula assignment for a ligand-protected Ag cluster of Ag 32(SG) 19.