Virtual Prototyping (VP) reproduces a complete machine to test it several times, as a scale 1:1 laboratory prototype. VP utilizes various CAE tools, such as 3D modelling, Structural FEA, Multibody Dynamic Analysis (MDA), Multiaxial fatigue analysis, and Fluid Structure Interaction (FSI) in an integrated way. The VP of a rotating machine allows considering a realistic stepless loading pattern throughout the complete revolution and determining automatically the fatigue safety factors within the whole machine structural assembly, while FSI allows dealing simultaneously with thermodynamic, motion and deformation phenomena. This approach was used to review the design of the crank mechanism and cylinders of an existing reciprocating compressor. The loads (including inertia forces) were applied to the gudgeon pin and, by means of the MDA, to all the other components. An advanced approach, based on Fluid Structure Interaction (FSI) analysis, was applied for the thermodynamic analysis of the cylinder’s efficiency. A 3D CFD Model, simulating the cylinder with mobile piston and valves, was developed and experimentally validated. The 3D domain simulating the compression chamber changes with the piston motion law while valve rings move according to the fluid dynamic forces.