The influence of particle size (20-200 nm) of Ag/α-Al 2O 3 catalysts for epoxidation of ethylene to ethylene oxide (EO) under industrial conditions was investigated. Small silver particles up to 40 nm are predominantly monocrystalline and show a decreasing weight-normalized reaction rate with increasing particle size. Particles larger than 50 nm consist of multiple silver crystallites with a much smaller domain size between 25 and 30 nm. For these polycrystalline silver particles, the weight-normalized reaction rate is independent of particle size. The ethylene conversion rate normalized to the external surface area increases when the silver particles become larger. We attribute this to a specific role of the grain boundaries between silver crystallites in supplying oxygen atoms to the external surface. Oxygen is likely activated at defects of an otherwise low-reactivity silver surface (for oxygen adsorption) followed by diffusion along grain boundaries, dissolution in the bulk, and diffusion to the external surface, where oxygen atoms react with ethylene. The reaction rate normalized to the surface area of the first outer shell of crystallites making up silver particles is independent of size for polycrystalline particles. A higher reaction pressure benefits ethylene oxidation rate and EO selectivity due to a higher oxygen coverage. Adding chlorine further improves the EO selectivity through modification of the active surface. The same particle size dependences are observed at 1 bar and at 20 bar without and with chlorine. The main finding of our work is that for large enough particles the ethylene oxidation rate normalized to the silver weight is independent of size. In addition to the size-independent weight-based activity, the preference for larger particles in industrial catalysts can be attributed to the high silver loadings used to obtain larger silver particles. The resulting high coverage of the α-Al 2O 3 support with silver decreases undesired consecutive reactions of EO on its hydroxyl groups.