The N-aryl- and N-acylguanidine structural motifs are essential for the function of several important classes of molecules, including pharmaceuticals, catalysts and natural products. Compounds combining both motifs can exist as different isomers due to tautomerism within the guanidine subunit, E/Z isomerism with reference to the guanidine double bond, and conformational isomerism. This complex phenomenon results in unresolved broad signal NMR spectra that strongly complicate the characterisation of these derivatives. Hence, the present study examines isomerism in N,N′-bis-aryl-N′′-acylguanidines using low temperature NMR spectroscopy in tandem with Density Functional Theory (DFT), Natural Bond Analysis (NBO) and the Gauge-Invariant Atomic Orbital (GIAO) approach for calculating the NMR chemical shifts associated with each isomer. It was found that the structural preference of these compounds is strongly influenced by intramolecular hydrogen bond (IMHB) effects.