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Supplemental Digital Content is available in the text.Summary:Early-onset carpal tunnel syndrome (CTS) is a well-known manifestation of mucopolysaccharidoses (MPS) due to excessive deposition of glycosaminoglycans in soft tissues. Standard treatment has been carpal tunnel release surgery, with the conventional technique of dividing the transverse carpal ligament. With advancement of treatments for MPS, these patients now have a longer life expectancy and are presenting with recurrent CTS. Management of recurrent CTS in these patients is not well studied. Here, we report 2 cases of recurrent CTS in MPS patients after a carpal tunnel release operation. We describe the findings on repeat operations and propose a unique technique for treating CTS in MPS patients to minimize recurrence during the initial CTS surgery. Our method involves resection of a portion of the transverse carpal ligament and use of a hypothenar fat pad flap over the median nerve.