We report analyses of cognitive function from siblings with MPS II enrolled in clinical trials: a natural history study (NCT01822184), a randomized, open‐label, phase 2/3 study of intravenous (IV) idursulfase with or without intrathecal idursulfase (idursulfase‐IT; NCT02055118), and its extension (NCT2412787). Here, IDS is linked to mucopolysaccharidosis type 2.