Recently, vector-borne diseases have been resurging in endemic areas and expanding their geographic range into nonendemic areas. Such changes have refocused attention to the potential for major public health events, as naive populations are exposed to these pathogens. Personal topical repellents, recommended by the United States Centers for Disease Control and Prevention and World Health Organization, remain a first line of protection against infection. The current study evaluated the repellent efficacy of four new U.S. Environmental Protection Agency-registered topical repellent products, two with picaridin as the active ingredient and two with IR3535, against a standard DEET (N,N-diethyl-3-methylbenzamide)-based product. All products were evaluated against a wide range of vector species under field conditions across the Americas. Human volunteers were used to evaluate product efficacy as compared with a well-known DEET-based formulation and determine suitability for use by the U.S. military. Findings demonstrated the new formulations performed as well as the standard U.S. military repellent and could be recommended for use.