Deterioration of intrinsic activity of Ir-based electrocatalysts during the oxygen evolution reaction (OER) has received much less attention compared to the metal dissolution. Combining chronoamperometry with operando electrochemical impedance spectroscopy and cyclic voltammetry, we show that the deactivation via active site phase transformation from hydrous Ir oxide/hydroxide into anhydrous Ir oxide, is concomitant with the dissolution-induced loss of electrochemical surface area. The relative contributions from these deactivation paths were found to be structure sensitive. Systematic evaluation of different Ir-based catalysts at identical electro-oxidative conditions showed that hydrous IrOx with structural short-range order exhibited an initial minor degradation of intrinsic activity but the most significant dissolution after the extended stability test. In contrast, newly-reported Ir superstructures with higher crystallinity and larger proportion of low-index crystal terminations exhibited enhanced resistance to dissolution but a major degradation of intrinsic activity, as the performance-relevant hydrous oxide/hydroxide species developed only on the surface of metallic Ir. The Ir/IrOxcatalyst regeneration was demonstrated. © 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license.