Systematic methods that speed-up the assignment of absolute configuration using vibrational circular dichrosim (VCD) and simplify its usage will advance this technique into a robust platform technology. Applying VCD to pharmaceutically relevant compounds has been handled in an ad hoc fashion, relying on fragment analysis and technical shortcuts to reduce the computational time required. We leverage a large computational infrastructure to provide adequate conformational exploration which enables an accurate assignment of absolute configuration. We describe a systematic approach for rapid calculation of VCD/IR spectra and comparison with corresponding measured spectra and apply this approach to assign the correct stereochemistry of nine test cases. We suggest moving away from the fragment approach when making VCD assignments. In addition to enabling faster and more reliable VCD assignments of absolute configuration, the ability to rapidly explore conformational space and sample conformations of complex molecules will have applicability in other areas of drug discovery.