PURPOSE: The epidemiology of carpal tunnel syndrome (CTS) has been extensively researched. However, data describing the economic burden of CTS is limited. The purpose of this study was to quantify the disease burden of CTS and determine the economic benefit of its surgical management. METHODS: A retrospective review of a Medicare database within the PearlDiver Supercomputer (Warsaw, IN) was performed for patients undergoing open (OCTR) or endoscopic carpal tunnel release (ECTR) from 2005–2012. The PearlDiver database is a publicly available Health Insurance Portability and Accountability Act (HIPAA)-compliant national database compiled from a collection of private payer records. This database contains current procedural terminology (CPT) and International Classification of Diseases, Ninth Revision (ICD-9) codes. Patients who underwent OCTR were identified by Current Procedural Terminology CPT-64721 and International Classification of Disease ICD-9 code 04.43. ECTR was identified by CPT-29848. CTS was identified by ICD-9 354.0. This data was used to calculate the total number of disability-adjusted life years (DALYs) associated with CTS. A human capital approach was employed and gross national income per capita was used to calculate the economic burden. RESULTS: From 2005–2012 there were 1,500,603 individuals identified in the Medicare patient population with the diagnosis of CTS. Untreated, this results in 804,113 DALYs without age weighting and discounting and 450,235 DALYs with age weighting and a discount rate of 3%. This amounts to between $21.8 and $39 billion in total economic burden, or $2.7 to $4.8 billion per year. 507924 patients underwent open carpal tunnel release (OCTR), while 68,768 underwent endoscopic carpal tunnel release (ECTR). Surgical management of CTS has resulted in the aversion of 138,000–290,000 DALYs. This has yielded between $800 million and $1.8 billion in economic benefit per year. Average cost per patient was $3,820 and $2,952 for OCTR and ECTR respectively. ECTR resulted in greater economic benefit per patient ($11,602-$23,042) than OCTR ($10,734-$22,174). CONCLUSION: CTS is prevalent in the Medicare patient population, and is associated with a large amount of economic burden. The surgical management of CTS leads to a large reduction in this burden, yielding extraordinary economic benefit. ECTR has a lower cost than OCTR, which results in greater economic benefit per patient if examining DALYs averted. A cost-effectiveness study using current cost data would provide greater insight into the economic aspects of CTS management.