A new, simple chiral HPLC method was developed for the enantiomeric separation of Levetiracetam, [( S)-α-ethyl-2-oxo-pyrrolidine acetamide], an antiepileptic drug in pharmaceutical formulations and in bulk materials. Enantiomeric separation was achieved on a chiralpak AD-H column using a mobile phase consisting of hexane and isopropanol in the ratio (90:10, v/v) at a flow rate of 1.0 ml/min. The resolution between the enantiomers was found to be not less than 7 in the optimized method. Interestingly, unwanted enantiomer, namely R-α-ethyl-2-oxo-pyrrolidine acetamide (( R)-enantiomer), was eluted prior to its mirror image in the developed method. The developed method was found to be selective in the presence of related impurities of Levetiracetam, namely N-(1-carbamoyl-propyl)-4-chloro-butyramide (Imp-1) and 1-ethyl-2-oxo-1-pyrrolidine acetic acid (Imp-2), and also under exposed conditions of UV light and 60 °C. The limit of detection (LOD) and limit of quantification (LOQ) of ( R)-enantiomer were found to be 900 and 2250 ng/ml, respectively, for 10 μl injection volume. The method precision for ( R)-enantiomer at limit of quantification level was within 8% R.S.D. Calibration curve for ( R)-enantiomer was linear over the studied ranges (2250–9000 ng) with correlation coefficient greater than 0998. The active pharmaceutical ingredient was extracted from its finished dosage form (tablet) using isopropanol. The percentage recoveries of ( R)-enantiomer were ranged from 94.2 to 102.6 and from 93.5 to 104.1 in spiked bulk and formulation samples of Levetiracetam, respectively. Levetiracetam sample solution and mobile phase are found to be stable for at least 48 h. The developed method was found to be rugged and robust. The proposed method was found to be suitable and accurate for the quantitative determination of ( R)-enantiomer in bulk drugs and commercial formulations. Chiralcel OD-H column can also be used as an alternative column for the above purpose.