The configurational and conformational structure of alfentanil hydrochloride (1) was studied by nuclear magnetic resonance and theoretical calculations. Compound 1 is best described by equilibrium between two stereoisomeric piperidinium rings with the N-substituent always being in equatorial position. Nuclear magnetic resonance spectra demonstrate that, depending on the solvent, 1 adopts the conformation with an axial methoxymethylene group. Computations were crucial in determining the importance of the transannular attractive interaction between the positive charge at the piperidinium N-atom and the methoxymethyl group in position 4.