A theoretical investigation of proton-coupled electron transfer in ruthenium polypyridyl complexes is presented. The three reactions studied are as follows: (1) the comproportionation reaction of [(bpy)(2)(py)(RuO)-O-IV](2+) and [(bpy)(2)(py)(RuOH2)-O-II](2+) to produce [(bpy)(2)(py)(RuOH)-O-III](2+); (2) the comproportionation reaction of [(tpy)(bpy)(RuO)-O-IV](2+) and [(tpy)(bpy)(RuOH2)-O-II](2+) to produce [(tpy)(bpy)(RuOH)-O-III](2+); and (3) the cross reaction of [(tpy)(bpy)(RuOH)-O-III](2+) and [(bpy)(2)(py)(RuOH2)-O-II](2+) to produce [(tpy)(bpy)(RuOH2)-O-II](2+) and [(bpy)(2)(py)(RuOH)-O-III](2+). This investigation is motivated by experimental measurements of rates and kinetic isotope effects for these systems (Binstead, R. A.; Meyer, T. J. J. Am. Chem. Soc. 1987, 109, 3287. Farrer, B. T.; Thorp, H. H. Inorg. Chem. 1999, 38, 2497.), These experiments indicate that the second reaction is nearly one order of magnitude faster than the first reaction, and the third reaction is in the intermediate regime. The experimentally measured kinetic isotope effects for these three reactions are 16.1, 11.4, and 5.8, respectively. The theoretical calculations elucidate the physical basis for the experimentally observed trends in rates and kinetic isotope effects, as well as for the unusually high magnitude of the kinetic isotope effects. In this empirical model, the proton donor-acceptor distance is predicted to be largest for the first reaction and smallest for the third reaction, This prediction is consistent with the degree of steric crowding near the oxygen proton acceptor for the three reactions. The second reaction is faster than the first reaction since a smaller proton donor-acceptor distance leads to a larger overlap between the reactant and product proton vibrational wave functions. The intermediate rate of the third reaction is determined by a balance among several competing factors. The observed trend in the kinetic isotope effects arises from the higher ratio of the hydrogen to deuterium vibrational wave function overlap for larger proton donor-acceptor distances. Thus, the kinetic isotope effect increases for larger proton donor-acceptor distances, The unusually high magnitude of the kinetic isotope effects is due in part to the close proximity of the proton transfer interface to the electron donor and acceptor. This proximity results in strong electrostatic interactions that lead to a relatively small overlap between the reactant and product vibrational wave functions.