Unraveling the native structure of protein-ligand complexes in solution enables rational drug design. We report here the use of 19F pseudocontact shift (PCS) NMR as a method to determine fluorine positions of high affinity ligands bound within the drug target human carbonic anhydrase II with high accuracy. Three different ligands were localized within the protein by analysis of the obtained PCS from simple one-dimensional 19F spectra with an accuracy of up to 0.8 Å. In order to validate the PCS, four to five independent magnetic susceptibility tensors induced by lanthanide chelating tags bound site-specifically to single cysteine mutants were refined. Least-squares minimization and a Monte-Carlo approach allowed the assessment of experimental errors on the intersection of the corresponding four to five PCS isosurfaces. By defining an angle score that reflects the relative isosurface orientation for different tensor combinations, it was established that the ligand can be localized accurately using only three tensors, if the isosurfaces are close to orthogonal. For two out of three ligands, the determined position closely matched the X-ray coordinates. Our results for the third ligand suggest, in accordance with previously reported ab initio calculations, a rotated position for the difluorophenyl substituent, enabling a favorable interaction with Phe-131. The lanthanide-fluorine distance varied between 22 and 38 Å and induced 19F PCS ranged from 0.078 to 0.409 ppm, averaging to 0.213 ppm. Accordingly, even longer metal-fluorine distances will lead to meaningful PCS, rendering the investigation of protein-ligand complexes significantly larger than 30 kDa feasible.