The aim of this work was to evaluate the compatibility between dipyrone, caffeine and orphenadrine citrate, active pharmaceutical ingredients (APIs) commonly used in fixed-dose combination (FDC) in analgesic medicines. The APIs were analyzed by Differential Scanning Calorimetry (DSC), Differential Thermal Analysis (DTA), Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Powder Diffraction (XRPD). DSC evaluated the heat and temperature of thermal events of APIs. Physical binary and ternary mixtures in the mass ratio of 1:1 and 1:1:1 were analyzed by DTA and showed only overlap of the peaks. DSC photovisual showed various phase transition processes with complete decomposition. FTIR and XRPD of binary and ternary mixtures showed no change in the profiles of APIs and the study showed that the APIs can be inserted in the same formulation.