Abstract The paper provides a methodology for the techno-economic optimization of microgrid systems and its application on the case study of St. Mary Lacor hospital of Gulu, Uganda. The low reliability of the Ugandan national grid represents a barrier for the operation of the infrastructures in the hospital and leads to extra costs for back-up solutions. Authors performed a two months data collection campaign, then the electrical load of the hospital has been simulated adopting two hundred realistic profiles obtained by means of a Monte Carlo procedure based on an on-site survey. Such data has been adopted in order to design a theoretical new microgrid capable to optimally feed the loads operating both in a grid tied and in a stand-alone configuration. One of the main goals of the microgrid is in the maximization of the energy supply reliability. The optimization method developed is based on the Poli.NRG tool, developed by Politecnico di Milano; it defines the optimal size of the system components as well as their dispatch strategy. The numerical results of the simulation could be adopted by the Hospital managers in order to evaluate new generators to be deployed in the facility and to identify the best energy policy.