This paper aims to analyse the mechanical properties response of polylactic acid (PLA) parts manufactured through fused filament fabrication. The influence of six manufacturing factors (layer height, filament width, fill density, layer orientation, printing velocity, and infill pattern) on the flexural resistance of PLA specimens is studied through an L27 Taguchi experimental array. Different geometries were tested on a four-point bending machine and on a rotating bending machine. From the first experimental phase, an optimal set of parameters deriving in the highest flexural resistance was determined. The results show that layer orientation is the most influential parameter, followed by layer height, filament width, and printing velocity, whereas the fill density and infill pattern show no significant influence. Finally, the fatigue fracture behaviour is evaluated and compared with that of previous studies’ results, in order to present a comprehensive study of the mechanical properties of the material under different kind of solicitations.