Turboprop aircraft achieve higher propulsive efficiencies at lower speeds due to their engine’s ability to accelerate a high mass flow of air at low jet velocities. With the increased importance of environmental considerations in aircraft design, aircraft manufacturers are forced to open up the considered speed domain since a reduction in cruise speed can lead to savings in fuel consumption and carbon dioxide emissions. Therefore, it becomes increasingly relevant to investigate the potential benefits of applying turboprop engines in regional aircraft design. It is the objective of this research study to explore the regional aircraft design space of direct operating cost and Mach number by performing multi-disciplinary optimization on both turboprop and turbofan aircraft configurations while including mission profile parameters as design variables. In total, three regional aircraft configurations are considered in this master thesis, differentiating themselves based on the configuration lay-out and type of engine application: a low-wing turbofan, a high-wing turbofan and a high-wing turboprop configuration. The latter configuration requires the implementation of a methodology to size, locate and scale the nacelle, where no landing gear is stored, while the leading-edge high lift devices for both high-wing configurations are redefined to accommodate the engine presence in front of the wing. All aircraft configurations are equipped with an advanced engine concept, having an entry-into-service year of 2025. Furthermore, a range equal to 1950 nautical miles and a payload of 70 passengers are imposed on all regional aircraft configurations. At the same time, three off-design missions are constructed in order to assess the range sensitivity of the design space. Due to the variety in encountered cruise Mach numbers and altitudes throughout this study, a method is introduced to determine the mission profile parameters of an aircraft design, cruising at any possible combination of Mach number and altitude. Next to the definition of the regional aircraft configurations and the mission requirements, a model is developed within a multi-disciplinary optimization environment, able to evaluate the performance of turboprop engines by means of a Fortran code which predicts the propeller efficiency at every flight condition. After having validated the developed model, empirical relationships to estimate the propeller mass and engine maintenance cost are added, resulting from an assessment of different methodologies. Also, an approximation of a take-off strategy to improve the field performance of the high-wing turboprop configuration is implemented, based on a ‘rolling take-off’ procedure where the power setting is gradually increased during take-off. For a baseline fuel cost of 3 dollars per gallon, the optimal design for each range is found to be a low-wing turbofan configuration, operating at or near Mach 0.80. At a range equal to 1950 nautical miles, a 4.5% advantage in direct operating cost is achieved by this configuration compared to the most optimal high-wing turboprop design. When the fuel price is simulated to increase, the minimum direct operating cost design among all ranges shifts to the high-wing turboprop configuration, exemplified by a 3.8% decrease in direct operating cost over the most optimal low-wing turbofan design, for a fuel price of 6 dollars per gallon and a range equal to 300 nautical miles. It is therefore concluded that a potential for turboprop applications exists in regional aircraft design, considering the expected rise in fuel cost over the next years.