We determined the distribution coefficients of solutes between a polymer film phase (polyvinyl chloride (PVC) with 67% (w/w) dioctyl sebacate (DOS)) and an aqueous phase in a 96-well format. The parallel measurement approach is efficient and uses very little material. Polymer–water distribution coefficients (Dpw) at different pH values yield the pKa and polymer–water partition coefficient values (Ppw) of the solutes. logPpw of a prominent drug-like compound, 2H-1,2,6-thiadiazine, 3-methyl-5-phenyl-,1,1-dioxide, is in good agreement with clogP, while the pKa value is substantially different from calculated values. This method has been also successfully applied to a library of novel drug-like compounds. logDpw values (at pH 4.0, 7.0, 10.0) of 24 novel drug-like compounds have been determined with good reproducibility with the 96-well plate approach. Differences between experimental values and a variety of available calculated values are significant. This emphasizes the need for laboratory separations-based measurements of logD.