Vibrational absorption and vibrational circular dichroism spectra (VA and VCD) have been recorded for two hybrid isoindolinone-phtalide stereoisomers dissolved in CDCl3. Density-functional calculations have been performed to determine their absolute configuration. A comparison of calculated and measured values has been made using several goodness-of-fit indicators, and also introducing a model-averaging technique, taking into account the variation of calculated spectra with the details of the computational method. The model-averaging technique, preliminarily tested on two VCD spectra already assigned to two diastereomers of tadalafil, gives higher credibility to the ab initio calculations, and should be useful for other molecules with high flexibility and/or more than one stereogenic center.