Bone substitute materials can replace damaged bone structures and significantly reduce the surgery and recovery times. Three-dimensional (3D) printing is a new rapid method to make these substitutes with exact shape and structure, based on actual individual bones medical measurement data. The goal of this work was to investigate the influence of the printing orientation on the smoothness and the percentage of void volume on the mechanical properties of biocompatible and biodegradable thermoplastic materials that can be applied for three-dimensional printing of human bone structure substitutes. Fused Deposition Modeling (FDM) is used to produce 3D printed shapes of bones created from DICOM images of CT and MRI scans. Three samples of acrylonitrile butadiene styrene (ABS) were printed utilizing or having different number of layers. That is, one, two and three layers at a 45º (head angle) were printed. The angle is related to the direction of the printing, which is controlled automatically by MakerWare software of the 3D printer itself, without any external control from the operator or technician. Thickness and roughness for each sample were subsequently measured. One sample of polylactic acid (PLA) was printed with one layer at 45º and its thickness and roughness were measured. Two other samples of ABS, having one and two layers, were printed at 90º then thickness and smoothness were measured. Polyvinyl alcohol (PVA) was printed with one layer at 45° and 90º. Thickness and roughness of printed 3D samples were measured using a White Light Interferometer.