Pretranslating input/output buffers in environments with multiple page sizes that include determining a pretranslation page size for an input/output buffer under an operating system that supports more than one memory page size, identifying pretranslation page frame numbers for the buffer in dependence upon the pretranslation page size, pretranslating the pretranslation page frame numbers to physical page numbers, and storing the physical page numbers in association with the pretranslation page size. Typical embodiments also include accessing the buffer, including translating a virtual memory address in the buffer to a physical memory address in dependence upon the physical page numbers and the pretranslation page size and accessing the physical memory of the buffer at the physical memory address.