Structural analysis of 17 methyl-substituted cyclopentanones (CPOs) was conducted using 2 + 1 resonance-enhanced multiphoton ionization (REMPI) spectroscopy via the 3s Rydberg state. The sharp spectra obtained with supersonically cooled samples show that methyl substitution leads to transition origin shifts with respect to CPO which depend on the position and orientation of the methyl group. Furthermore, multiple methyl substitutions give rise to shifts that are nearly equal to the addition of composite monomethyl shifts. Molecular mechanics and ab initio molecular orbital calculations indicate that CPO and most of the methyl-substituted derivatives have twisted geometries. The calculated potential energy barrier between various conformations was found to be no greater than 2.0 kcal/mol for the methyl-substituted derivatives, which is considerably smaller than the 3.8 kcal/mol barrier in unsubstituted CPO. One molecule, cis-2,5-dimethyl CPO, is predicted to be stable only in an envelope (bent) form, while others were found to have stable envelope and twist potential wells. A correlation was found between the 3s <-- n REMPI spectra and C-13 NMR carbonyl carbon chemical shifts. The C-13 NMR shifts could be calculated from local van der Waals energies and electrostatic potentials at the carbonyl carbon. It was possible to calculate the energy of the 3s excited state from these nonbonded interactions on the basis of the observed correlation.