Fluorescence excitation spectrum of jet-cooled acetaminophen was obtained. When AAP was expanded with a buffer gas containing 0.3-1.1% of water, absorption peaks of the less stable trans conformer was significantly reduced by solvent-assisted conformational isomerization (SAC), which is confirmed by a separately measured UV-UV hole burning spectroscopy. It is also confirmed by quantum mechanical calculation and RRKM calculation that it is energetically and kinetically possible to induce SACI in AAP with water. The SACI mechanism suggests a possible pathway that acetaminophen can adopt an active conformation in vivo, which is need for molecular recognition and drug activity. (C) 2013 Elsevier B.V. All rights reserved.