The disposal of infectious waste remains one of the most severe medical, social, and environmental problems in almost every country. Choosing the right location and arranging the most suitable transport route is one of the main issues in managing hazardous waste. Identifying a site for the disposal of infectious waste is a complicated process because both tangible and intangible factors must be considered together, and it also depends on various rules and regulations. This research aims to solve the problem of the size selection and location of infectious waste incinerators for 109 community hospitals in the upper part of northeastern Thailand by applying a differential evolution algorithm to solve the problem with the objective of minimizing the total system cost, which consists of the cost of transporting infectious waste, the fixed costs, and the variable cost of operating the infectious waste incinerator. The developed differential evolution produces vectors that differ from the conventional differential evolution. Instead of a single set of vectors, three are created to search for the solution. In addition to solving the problem of the case study, this research conducts numerical experiments with randomly generated data to measure the performance of the differential evolution algorithm. The results show that the proposed algorithm efficiently solves the problem and can find the global optimal solution for the problem studied.