In this work a streamlined design process of a machining centre spindle assembly is advocated in a flexible, yet standardised manner. This enables automatic construction of a structured 3D mesh, following a consistent numbering scheme of mesh regions so as to automate load application (bearings reactions and machining force) in parametrically variable spindle models. In this way, numerical analysis of any desired range of candidate design variants can be performed. Two groups of parameters are considered in spindle modelling: design and functional. Important design parameters are: number of bearings, bearings span and spindle diameters. A Design of Experiments (DoE) orthogonal array is a good way to discover favourable combinations of design parameter values as well as their relative importance through modal analysis without exhausting all possible combinations. Important functional parameters are: rotation speed and machining force pattern. Their effect is explored by transient dynamic analysis for targeted loading scenarios studying deflection at points of interest such as tool tip, bearings interface, coupling interface etc. Illustrative examples are given concerning 18 variants of a typical machining centre spindle.