Simulation of the first cycle of the DEPA-TOPO process of uranium recovery from wet-process phosphoric acid with mixer-settler contactors operated in a counter-current (CTC), cross-current (CSC) and an alternative extraction-stripping (AES) flow arrangement (FA) was done. The simulation was performed for the cases when the equilibrium relationships are linear in the extraction and stripping section as well as non-linear in the stripping section. In order to get the equilibrium relationships, the DEPA-TOPO process was simulated in separation funnels using representative phosphoric acid samples taken from a fertilizer company. The Murphree stage efficiencies (for the extraction section for the aqueous phase, EMx, and for the stripping section EMx(s)) were taken into account in the model. As far as the recovery is concerned, CSCFA is better than other FAs. The same number of stages in the extraction and the stripping section is better than other combinations if the total number of stages is constant. For the CTCFA, there is an optimum of the organic-to-aqueous flow rate. This value depends on the extraction and stripping isotherms slopes (E and E-s coefficients, EMx and EMx(s) stage efficiencies, and, in the case of non-linear stripping isotherm, on the inlet uranium concentration).