The recent increase in research and applications of oligonucleotides in new drug design has stimulated a need to determine the three-dimensional structures of oligonucleotides and their complexes with various ligands. Three-dimensional structure determination relies on X-ray diffraction data from high-quality crystals. However, only a very limited number of RNA molecules have been crystallized, and a broad record of experience in oligonucleotide crystallization is lacking. Osmotic dewatering is a crystallization method in which the oligonucleotide and its precipitant are concentrated at a controlled rate by the removal of water through a reverse-osmosis membrane using a specified concentration gradient. Therefore, rates of nucleation and crystal growth can be controlled. In this study, a transport model was developed to predict the water removal rates at various concentration gradients. Experimental dewatering rate data agreed very well with theoretical calculations. Model predictions were applied to different osmotic dewatering crystallization devices to crystalize a model RNA, "U-U dodecamer". High-quality dodecamer crystals were successfully grown and yielded a maximum X-ray diffraction resolution of 2.46 Angstrom and usable resolution of 3.0 Angstrom. The results of this research will facilitate the applications of osmotic dewatering to crystallographic studies and industrial purification of biopharmaceuticals.