The role of surgical intervention for carpal tunnel syndrome (CTS) and trigger digits in children with mucopolysaccharide storage disorders (MPSDs) has not been clearly defined, particularly as the treatment of the underlying disease has advanced to include bone marrow transplantation. This study reviews our experience in the treatment of CTS and trigger digits in 22 children with MPSDs who were evaluated for CTS by electromyographic (EMG)/nerve conduction velocity (NCV) testing. Seventeen children were diagnosed with CTS by EMG/NCV testing and were treated with bilateral open surgical release with or without flexor tenosynovectomy. The EMG/NCV testing revealed normal results in 5 patients who are subsequently being monitored. Forty-five digits in 8 children were diagnosed clinically with trigger digits. Nineteen digits were treated by annular pulley release alone. Twenty-six digits were treated by annular pulley release with partial flexor digitorum superficialis tendon resection. The average age at the time of hand surgery was 6.3 years, and at the time of follow-up, 9.6 years. Postoperative EMG/NCV testing in 7 children showed 1 with improvement and 6 with normalization. None of the patients undergoing carpal tunnel release went on to develop thenar atrophy or absent sensibility, as has been reported in untreated cases. Patients were evaluated for triggering digits both by preoperative tendon palpation and by intraoperative flexor tendon excursion at the time of open carpal tunnel release. All patients undergoing trigger release had improved active digital flexion seen at the final follow-up visit. Because of the very high incidence of CTS and trigger digits in this population, the authors currently recommend routine screening of EMG/NCV for all children with MPSDs. Early surgical intervention for nerve compression and stenosing flexor tenosynovitis can maximize hand function in these children.