Abstract Tautomerism, aromaticity, and electron density at ring critical points of substituted benzodiazepinones, composed of condensed 6- and 7-membered rings (7-substituted 1,3-dihydro-benzo[e][1,4]diazepin-2-ones), were studied at the B3LYP/6-31G ∗∗ level. We found that in the gas phase and in water, the N1H tautomers are more stable than the N4H ones by at least 8 kcal/mol. We have demonstrated that the greater the π-electron donation of the substituent, the more stable the N1H tautomer. Analysis of the HOMA index of the two rings shows that in the N1H tautomers, the benzo ring is aromatic and the diazepinone ring is antiaromatic. In the N4H tautomers the former ring loses aromaticity and the latter one gains a more antiaromatic character. This is the main reason for the relative instability of the N4H tautomers. The AIM analysis combined with the substituent effect analysis by use of the sEDA and pEDA descriptors reveal that the π-electron properties of the substituents attached to the 6-membered benzo ring linearly correlate with the electron density and Laplacian at ring critical point of the 7-membered diazepinone one. Surprisingly, the analogous correlation for the substituted at the 6-membered ring is far less significant, if it is significant at all. This strongly suggests that modification in pharmaceutical activity of benzodiazepinones can be partially controlled just by attaching a substituent of the proper π-electron donor–acceptor properties in the C7-position of the benzo ring.