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The pharmaceutical industry is now directed to the market of more safety and efficient drugs, based on single enantiomers. Ketoprofen, still used as a racemic pharmaceutical drug, belongs to the profens class, one of the most representative of the non-steroidal anti-inflammatory drugs. This work presents the chiral separation of ketoprofen enantiomers by simulated moving bed technology, using a laboratory scale unit (the FlexSMB-LSRE1) with six columns, packed with the Chiralpak AD1 stationary phase (20 lm). A comparative study between a mobile phase composed of a traditional high hydrocarbon content (10%ethanol=90%n-hexane=0- .01%TFA) and a strong polar organic composition (100%ethanol= 0.01%TFA) is presented. The study includes the measurement of the adsorption isotherms, elution, and frontal chromatography experiments, carried out on a SMB column for both compositions. The results obtained allowed the prediction and optimization of the SMB operation. Using pure ethanol as solvent and a racemic feed concentration of 40 g=L, purities above 98.6% on both outlet streams were obtained, with a productivity of 3.84 gfeed=(Lbed.hr) and a solvent consumption of 0.78Lsolvent=gfeed. The results obtained in the experimental separation of ketoprofen enantiomers by SMB chromatography indicates that pure ethanol presents better performances than the classic high hydrocarbon content composition.