PurposeCarpal tunnel syndrome is the most common compressive neuropathy. There is limited evidence to support endoscopic compared to open carpal tunnel release according to the 2016 American Academy of Orthopaedic Surgeons Clinical Practice Guideline on carpal tunnel syndrome. The purpose of the present study was to assess differences between the two procedures by comparing 30- and 90-day complications and mean hospital costs in a large patient population. MethodsUsing the national Mariner15 Database by PearlDiver Technologies, we retrospectively studied 27,192 carpal tunnel syndrome patients who received carpal tunnel release using an endoscopic or open surgical approach from 2010 to 2019. Patients who met the inclusion criteria were grouped and case-matched at a 1:1 ratio through the corresponding International Classification of Diseases codes (n = 13,596) and assessed for 30- and 90-day complications such as median nerve injury, superficial palmar arch injury, and revision carpal tunnel release surgery. Univariate analysis was used to compare outcomes and a multivariate regression was performed to identify risk factors associated with each outcome. ResultsEndoscopic carpal tunnel release was associated with a higher rate of median nerve injury than open release at 30 days (0.3% vs. 0.1% odds ratio, 2.21; 95% confidence interval, 1.29–3.81; p < 0.05) and 90 days (0.4% vs. 0.3%; odds ratio, 1.77; 95% confidence interval, 1.16–2.70; p < 0.05). Endoscopic release was also associated with a higher rate of superficial palmar arch injury (0.1% vs. 0%; odds ratio, 25.02; 95% confidence interval, 1.48–423.0; p < 0.05). ConclusionsIn the present study, risk of median nerve injury and vascular injury was higher after endoscopic than open carpal tunnel release. At 90 days, all-cause revision rates were similar between techniques. Surgeons should understand these differences, to optimize surgical decision-making. Level of evidenceTherapeutic, IIIa.