tUnderstanding the phase behavior of an active pharmaceutical ingredient in a drug formulation isrequired to avoid the occurrence of sudden phase changes resulting in decrease of bioavailability in amarketed product. Benzocaine is known to possess three crystalline polymorphs, but their stability hier-archy has so far not been determined. A topological method and direct calorimetric measurements underpressure have been used to construct the topological pressure–temperature diagram of the phase rela-tionships between the solid phases II and III, the liquid, and the vapor phase. In the process, the transitiontemperature between solid phases III and II and its enthalpy change have been determined. Solid phaseII, which has the highest melting point, is the more stable phase under ambient conditions in this phasediagram. Surprisingly, solid phase I has not been observed during the study, even though the scarce lit-erature data on its thermal behavior appear to indicate that it might be the most stable one of the threesolid phases.