Despite being an essential line of defense in preventing the spread of diseases, medical glove durability is neither measured routinely nor has standard specifications. In this study, a new glove durability assessment device is used to objectively compare the durability of gloves made of a variety of elastomers from different manufacturers. Results are related to several mechanical tests, including stress relaxation, tensile and tear tests. Overall, natural latex gloves far outperformed those made of synthetic elastomers, and there is great disparity among the different brands of nitrile gloves, some of which do not meet nitrile glove performance requirements. The study includes prototype gloves made from guayule latex, a domestic source of alternative natural rubber latex, currently under commercial development. The guayule gloves outperformed all other gloves tested, including those made from Hevea latex, without posing allergy risks. Mechanical analysis demonstrated that the guayule gloves are as strong as the best alternatives, are softer and more elastic, have better tear strength, and have such low stress relaxation that they cause very little hand fatigue during use. Guayule latex can address the need for domestic production of gloves to resolve supply chain and quality issues and encourage a shift back to natural latex gloves, which will significantly diversify the natural rubber supply.