Separation of steroids by liquid-liquid extraction with ionic liquids (ILs) as solvent was studied both experimentally and by simulation using a model mixture of progesterone and pregnenolone. The studies involved a solvent screening using COSMO-RS software for estimation of progesterone solubility. An experimental compatibility study of several solvents with reasonable progesterone solubility with several ILs. The results showed tert-butyl methyl ether (TBME)-butyl methyl imidazolium tetrafluoroborate (BMIM BE4) as the most promising solvent combination. Next, equilibrium partitioning of both progesterone and pregnenolone in this solvent combination was determined experimentally. Fixed bed studies using solvent impregnated resin (SIR) obtained by impregnation of BMIM BF4 in silica showed that it is feasible to obtain highly pure progesterone in such a process. However, the yield was far from quantitative and thus a fractional extraction process was studied by simulation of a counter current extraction process. The simulation study showed that with fractional extraction highly pure progesterone (excess >0.99) can be obtained at a yield of >0.95 when a minimum of 24 equilibrium stages are applied. (C) 2015 Elsevier B.V. All rights reserved.