A capillary electrophoresis (CE) method was developed for the stereoselective determination of the non-steroidal anti-inflammatory drug (NSAID), S-naproxen, in tablets. Several β-cyclodextrin derivatives (CDs) were tested as chiral selectors, including sulfobutyl- β-CD (SBCD), carboxymethyl- β-CD (CMCD), dimethyl- β-CD (DMCD) and trimethyl- β-CD (TMCD), in a phosphoric acid/triethanolamine pH 3 buffer. Under these conditions, the analyte was mainly present in an uncharged form and therefore, the use a neutral CD (DMCD or TMCD) alone could not lead to enantiomeric separation. On the contrary, by addition of a charged CD (SBCD or CMCD) to the running buffer, giving the analyte enantiomers an adequate mobility, chiral resolution could be achieved, although the resolution values obtained in this case were not quite satisfactory ( Rs<1.5). Dual systems, based on the use of mixtures of charged and neutral CDs, were then investigated. The SBCD/TMCD system was found to be particularly well suited to the enantioseparation of naproxen and after optimisation of the concentrations of both CDs, a resolution value of 5.4 could be obtained. The method was validated for the determination of R-naproxen (enantiomeric impurity) in the 0.1–2% range, using the racemic mixture of the analyte. A second validation was performed in the 50–150% range for the quantitation of S-naproxen. In both cases, good results with respect to linearity, precision and accuracy were obtained.