<p>The paper studies the optimization of interurban smart grid design by minimizing energy losses along the transmission lines. The optimized layout of the smart grid considers the location of the energy sources and consumption centers and the paths of the distribution lines. The optimization design includes the hourly distribution of the power sources and the hourly profile of the energy consumption. We developed a modeling study of the operation of a smart grid for specific operating conditions in a real case using historical data on electric energy consumption, solar, wind, and hydraulic energy resource. The study aims the development an algorithm that minimizes electric energy losses; this algorithm is based on the hourly distribution of energy generation and electric energy consumption but applies to other time intervals like days or seconds. The modelling results in a reduction of energy losses of 11.8%. This value corresponds to the selected configuration for this study; however, the methodology can be applied to any other grid configuration.</p>