Four commercially available lipases and two native lipases from Aspergillus niger AC-54 and Aspergillus terreus AC-430 were used for the resolution of (RS)-Ibuprofen in systems containing the ionic liquids [BMIM][PF 6 ] and [BMIM][BF 4 ]. The lipases showed higher conversion in a two-phase system using [BMIM][PF 6 ] and isooctane compared to that in pure isooctane. Although the best enzyme was a commercially available lipase from Candida rugosa (E=8.5), another native lipase, produced in our laboratory, from A. niger gave better enantioselectivity (E=4.6) than the other lipases tested (E=1.9–3.3.). After thorough optimization of several reaction conditions (type and ratios of isooctane/ionic liquid, amount of enzyme, and reaction time), the E-value of A. niger lipase (15% w/v) could be duplicated (E=9.2) in a solvent system composed of [BMIM][PF 6 ] and isooctane (1:1) after 96h of reaction.