Exceptional water oxidation (WO) turnover frequencies (TOF=17 000 h(-1) ), and turnover numbers (TONs) close to 400 000, the largest ever reported for a metal-catalyzed WO reaction, have been found by using [Cp*Ir(III) (NHC)Cl2 ] (in which NHC=3-methyl-1-(1-phenylethyl)-imidazoline-2-ylidene) as the pre-catalyst and NaIO4 as oxidant in water at 40 °C. The apparent TOF for [Cp*Ir(III) (NHC)X2 ] (1 X, in which X stands for I (1 I), Cl (1 Cl), or triflate anion (1 OTf)) and [(Cp*-NHCMe)Ir(III) I2 ] (2) complexes, is kept constant during almost all of the O2 evolution reaction when using NaIO4 as oxidant. The TOF was found to be dependent on the ligand and on the anion (TOF ranging from ≈600 to ≈1100 h(-1) at 25 °C). Degradation of the complexes by oxidation of the organic ligands upon reaction with NaIO4 has been investigated. (1) H NMR, ESI-MS, and dynamic light-scattering measurements (DLS) of the reaction medium indicated that the complex undergoes rapid degradation, even at low equivalents of oxidant, but this process takes place without formation of nanoparticles. Remarkably, three-month-old solution samples of oxidized pre-catalysts remain equally as active as freshly prepared solutions. A UV/Vis feature band at λmax =405 nm is observed in catalytic reaction solutions only when O2 evolves, which may be attributed to a resting state iridium speciation, most probably Ir-oxo species with an oxidation state higher than IV.