In the last years the numerical approach in the U isotopes separation process by centrifugation has grown in importance to prevent possible breaks and violations of Non Proliferation (NP) treaties. The Institute of Transuranium Elements of the Joint Research Centre has developed a numerical tool for the UF6 enrichment cascades simulation. The tool assumes a “quasi” ideal cascade structure and a single stage mixing coefficient that can be varied and adapted to the supplied experimental data when available. The work illustrates the characteristics of the model and its applications to some plant configurations at different enrichment stages. The theory for reproducing the fluid dynamics of the centrifuge is derived from the work of Cohen where the separation parameters are calculated using the solution of a differential enrichment equation. In our case we chose to solve the hydrodynamic equations for the motion of a compressible fluid in a centrifugal field using the Berman – Olander vertical velocity radial distribution. Once the separation parameters of the centrifuges are calculated, the countercurrent cascade is simulated with specific values of material flow rates and concentrations. Moreover the different hypothetical enrichment scenarios can be estimated based on a-specific set of flow parameters defined a priori. Despite inter-stage mixing is not allowed, the symmetric characteristics of the flows of the countercurrent cascades are broken by introducing the stage mixing coefficients ci in the formula connecting the head and the tails stage separation factors and . The stage mixing coefficients ci are calculated by means of an iterative numerical procedure based on advanced optimization techniques. For the current NP analyses of the worldwide enrichment activities, following the information supplied by IAEA, a large use of cascades model has been done. This paper illustrates some characteristics of the model and its applications to some plant configurations at different enrichment stage. The results are in good agreement and coherent with the experimental data reported and demonstrate the possibility to use the simulation as a valid additional tool when some information on the real plant performance is missing or is inaccurate.