This study demonstrates that ΔlogP(oct-tol) (difference between logP(octanol) and logP(toluene)) describes compounds propensity to form intramolecular hydrogen bonds (IMHB) and may be considered a privileged molecular descriptor for use in drug discovery and for prediction of IMHB in drug candidates. We identified experimental protocols for acquiring reliable ΔlogP(oct-tol) values on a set of compounds representing IMHB motifs most prevalent in medicinal chemistry, mainly molecules capable of forming 6-, 7-member IMHB rings. Furthermore, computational ΔlogP(oct-tol) values obtained with COSMO-RS software provided a good estimate of experimental results and can be used prospectively to assess IMHB. The proposed interpretation method based on ΔlogP(oct-tol) data allowed categorization of the compounds into 2 groups: with high propensity to form IMHB and poor propensity or poor relevance of IMHB. The relative (1)H NMR chemical shift of an exchangeable proton was used to verify presence of IMHB and to validate the IMHB interpretation scheme.