Application of thermogravimetry (TG) alone to study compatibility/incompatibility of active pharmaceutical ingredients (APIs) with excipients yields to misleading results due to overlapping of the thermal stages in the course of decomposition of both ingredients and their pharmaceutical mixtures. Hence, the purpose of this study was to assess the usefulness of multivariate statistical analysis as a supporting tool for interpretation of the TG traces during assessing compatibility of hydrocortisone as an API with selected excipients (mannitol, starch, lactose, methylcellulose, β-cyclodextrin, meglumine, chitosan, magnesium stearate and polyvinylpyrrolidone). The results show that two multivariate techniques, principal component analysis (PCA) and cluster analysis (CA), can be successfully used for interpretation of TG traces, while the TG is used alone as a screening technique to assess compatibility. The results obtained by using TG analysis, supported by PCA and CA, were approved by those of differential scanning calorimetry, infrared spectroscopy and X-ray powder diffraction. Incompatibilities were only found in mixtures of hydrocortisone with magnesium stearate and β-cyclodextrin.