Advanced materials are needed to meet the requirements of devices designed for harvesting and storing renewable electricity. In particular, polymer electrolyte membrane water electrolyzers (PEMWEs) could benefit from a reduction in the size of the iridium oxide (IrO_x) particles used to electrocatalyze the sluggish oxygen evolution reaction (OER). To verify the validity of this approach, we built a library of 18 supported and unsupported IrO_x catalysts and established their stability number (S-number) values using inductively coupled plasma mass spectrometry and electrochemistry. Our results provide quantitative evidence that (i) supported IrO_x nanocatalysts are more active toward the OER but less stable than unsupported micrometer-sized catalysts, for example, commercial IrO₂ or porous IrO_x microparticles; (ii) tantalum-doped tin oxides (TaTO) used as supports for IrO_x nanoparticles are more stable than antimony-doped tin oxides (ATO) and carbon black (Vulcan XC72); (iii) thermal annealing under air atmosphere yields depreciated OER activity but enhanced stability; (iv) the beneficial effect of thermal annealing holds both for micro- and nano-IrO_x particles and leads to 1 order of magnitude lower Ir atom dissolution rate with respect to nonannealed catalysts; (v) the best compromise between OER activity and stability was obtained for unsupported porous IrO_x microparticles after thermal annealing under air at 450 °C. These insights provide guidance on which material classes and strategies are the most likely to increase sustainably the OER efficiency while contributing to diminish the cost of PEMWE devices.