Abstract The determination of whether two stereoisomers constitute a pair of epimers or if they differ in their configuration at all stereogenic centers bar one can be a formidable challenge and represent a problem of greater complexity than just determination of absolute configuration per se. The latter case has been defined as a pair of inverse epimers and is exemplified by the naturally occurring compounds alnumycins A1–3. The potential of vibrational circular dichroism (VCD) for discerning between pairs of epimers or inverse epimers has been considered in principle for the alnumycin A1 pair and the C-1 epimer of A1α ( ent -A1β) by DFT-calculated spectra obtained at the M06-2X/6-31G(d) level of theory. It was concluded that the application holds much promise for the task at hand and can overcome the shortcomings associated with other techniques, in particular with respect to their limited generality.