The Z/E isomer ratios for codeinone-6-oxime and 7,8-dihydro-codeinone-6-oxime in chloroform and in a water: acetonitrile 85:15 (volume ratio) mixture have been theoretically calculated using the polarizable continuum method at the B3LYP/6-31G* level. Gas phase optimized geometries and thermal corrections were used for obtaining total relative free energies in solution. For validating the B3LYP/6-31G* calculations, optimized geometries and relative energies for the gas phase formaldoxime have been compared with values from B3LYP/6-311++G** calculations. B3LYP/6-31G* optimized geometric parameters are almost constant for formaldoxime, the C-ring model compound, (methoxy-methyl)vinyl-ketone oxime, and codeinone oximes in the absence of special structural features. Transition states, one for each, have been identified for the syn-anti and anti-anti transformations of formaldoxime. The energy and free energy of the barrier for the syn to anti rotation are 9.4 and 8.5 kcal/mol, respectively; the corresponding barrier values for the anti-anti isomerization were calculated at 55.1 and 53.7 kcal/mol. The Onsager approach of the solvent effect breaks down for such large systems as codeinone oximes. Using the self-consistent ab initio PCM approach, the smallest solvent effect has been calculated just for the molecule with the largest dipole moment. Polarization energies for codeinone-6-oximes are larger than those of the 7,8-dihydro derivatives. The larger polarization energies are accompanied with more negative solute-solvent interaction energies in both solvents. Isomer/ conformer compositions have been calculated on the basis of relative internal free energies and free energies of solvation. The frequency-dependent relative thermal correction is negligible for the anti-codeinone oximes, but the value is 0.66 kcal/mol for the Z/syn relative to the Z/anti conformer. In chloroform, the Z:E composition was calculated at 47.5:52.5 as compared to our experimental value of 69:31 from NMR measurements. In the water: acetonitrile mixture, the theoretical ratio is 65.7:34.3 as compared to 73:27 as determined by high-performance liquid chromatography. For 7,8-dihydro-codeinone-6-oxime, the calculated composition in chloroform is 92.4% E and 7.6% Z, and the theoretical values in the water/acetonitrile mixture are 93.9% E and 6.1% Z. Both predictions are close to the experimental finding that the E form is practically the only existing isomer in solution. The different Z/E relative stabilities for the codeinone-6-oxime and the 7,8-dihydro derivative are primarily attributed to a remarkable change in the geometry of the C-ring. Overall, PCM/B3LYP/6-31G* calculations can provide isomer/conformer equilibrium compositions in both nonpolar and aqueous solutions in fair agreement with experimental values.