Effective tissue preservation is key to obtaining high quality DNA for rigorous downstream analyses. DMSO-salt (DES) is a common tissue preservative comprised of three components: 20% DMSO (D), 0.25M EDTA (E), and saturated NaCl (S). This solution is practical for field use and sample transport, but both the DMSO and salt components have associated disadvantages. Despite these drawbacks, there has been no effort to determine the ability of the individual components of DMSO-salt to preserve DNA. Here, we determine the active ingredient(s) of DMSO-salt by comparing the percentage of high molecular weight (HMW) DNA recovered from tissue of three aquatic species (Mytilus edulis, Orconectes virilism, and Hediste diversicolor) preserved in eight different preservatives including DES, 95% EtOH, and six formulations comprised of components of DES (DE, DS, ES, D, E, and S). DNA was extracted from tissues stored at room temperature in preservative for between one day and six months. HMW DNA was recovered from all solutions containing both EDTA and NaCl after three months of preservation for all three species. Moreover, tissues treated with either DMSO alone, NaCl alone, or both DMSO and NaCl consistently failed to preserve HMW DNA, irrespective of taxa. This indicates that neither DMSO nor NaCl are likely the active ingredients in DMSO-salt and instead, we conclude that EDTA is the active ingredient. This suggests that researchers can remove DMSO from DMSO-salt and still reliably recover HMW DNA while reducing both financial costs and exposure to hazardous chemicals.