The influence of the microstructural arrangement of 3D-printed polylactic acid (PLA) on its mechanical properties is studied using both numerical and experimental approaches. Thermal cycling during the laying down of PLA filament is investigated through infra-red measurements for different printing conditions. The microstructure induced by 3D printing is determined using X-ray micro-tomography. The mechanical properties are measured under tensile testing conditions. Finite element computation is considered to predict the mechanical performance of 3D-printed PLA by converting the acquired 3D images into structural meshes. The results confirm the leading role of the printing temperature on thermal cycling during the laying down process. In addition, the weak influence of the printing temperature on the stiffness of 3D-printed PLA is explained by the relatively small change in porosity content. However, the influence of the printing temperature on the ultimate properties is found to be substantial. This major influence is explained from finite element predictions as an effect of pore connectivity which is found to be the control factor for tensile strength.