The increasing scarcity of iridium (Ir) and its rutile-type oxide (IrO 2 ), the current state-of-the-art oxygen evolution reaction (OER) catalysts, is driving the transition toward the use of mixed Ir oxides with a highly active yet inexpensive metal (Ir x M 1−x O 2 ). Ruthenium (Ru) has been commonly employed due to its high OER activity although its electrochemical stability in Ir-Ru mixed oxide nanoparticles (Ir x Ru 1−x O 2 NPs), especially at high relative contents, is rarely evaluated for long-term application as water electrolyzers. In this work, we bridge the knowledge gap by performing a thorough study on the composition-and phase-dependent stability of welldefined Ir x Ru 1−x O 2 NPs prepared by flame spray pyrolysis under dynamic operating conditions. As-prepared NPs (Ir x Ru 1−x O y ) present an amorphous coral-like structure with a hydrous Ir-Ru oxide phase, which upon post-synthetic thermal treatment fully converts to a rutile-type structure followed by a selective Ir enrichment at the NP topmost surface. It was demonstrated that Ir incorporation into a RuO 2 matrix drastically reduced Ru dissolution by ca. 10-fold at the expense of worsening Ir inherent stability, regardless of the oxide phase present. Hydrous Ir x Ru 1−x O y NPs, however, were shown to be 1000-fold less stable than rutile-type Ir x Ru 1−x O 2 , where the severe Ru leaching yielded a fast convergence toward the activity of monometallic hydrous IrO y . For rutiletype Ir x Ru 1−x O 2 , the sequential start-up/shut-down OER protocol employed revealed a steady-state dissolution for both Ir and Ru, as well as the key role of surface Ru species in OER activity: minimal Ru surface losses (<1 at. %) yielded OER activities for tested Ir 0.2 Ru 0.8 O 2 equivalent to those of untested Ir 0.8 Ru 0.2 O 2 . Ir enrichment at the NP topmost surface, which mitigates selective subsurface Ru dissolution, is identified as the origin of the NP stabilization. These results suggest Ru-rich Ir x Ru 1−x O 2 NPs to be viable electrocatalysts for long-term water electrolysis, with significant repercussions in cost reduction.