The photophysical properties of Piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), were investigated at different pH_ext values in reversed micelles of Aerosol-OT (AOT) in iso-octane, using both steady-state and picosecond time-resolved fluorescence spectroscopy. In contrast with the very complex data obtained in aqueous media, where several prototropic species are in equilibrium, the reversed micellar system essentially favors two species. The absorption spectra shows only one isosbestic point at λ = 348 nm. Excited-state intramolecular proton transfer (ESIPT), also detected in water, is promoted at low water pool contents measured by ω₀ = [H₂O]/[AOT]. A strongly shifted (λ_em = 470 nm) tautomeric emission is found. Upon the gradual increase of ω₀, striking differences with pH_ext are found. At pH_ext = 4, the drug preferentially locates itself in the interfacial region partitioning between a hydrophobic and a hydrophilic domain. Global analysis was applied to the decay data and the results were interpreted by the “two-state excited-state” formalism. At pH_ext = 7, the anionic species is prevalent and the probe locates itself deeper inside the water core of the reversed micelles. Thus, a strong dependence on water content is detected, approaching a behavior similar to that observed in free aqueous solutions.