Purpose Pain, allodynia, and stiffness in complex regional pain syndrome (CRPS) greatly affects social, vocational, and community engagement. The aim of this study was to evaluate the effect of isolated median nerve releases on the outcome of CRPS 1 of the hand. Methods In this prospective case series, people of any age diagnosed with and treated for CRPS 1 of the upper limb attending the author's practice were consecutively recruited. All were self-referrals dissatisfied with the treatment provided previously. Only patients who had been treated with nerve release to control their symptoms were included. Primary outcome measures were pain and Disabilities of the Arm, Shoulder, and Hand score. A secondary outcome was withdrawal from pain medication. Full resolution was defined as 0 pain, on a scale of 0-10, and total withdrawal from pain medication at the latest follow-up. Results Between January 2018 and December 2022, 82 participants with CRPS 1 of the hand for an average of 20 months were evaluated. Eighty-five nerve releases were performed. As per protocol, carpal tunnel release was performed in all, and three patients also received an endoscopic pronator release. Minor procedures unrelated to the pain were carried out concomitantly in 17 patients. Significant improvements were observed in pain score (mean 8.9 +/- 1.2 at baseline vs 0.6 +/- 1.8 at 35 months) and in Disabilities of the Arm, Shoulder, and Hand score (82 +/- 13 vs 13 +/- 20) for the same period. Five patients (6%) were considered failures. In contrast, 65 patients (79%) had full resolution of their symptoms. Conclusions This study demonstrates that a large percentage of patients diagnosed with and treated for CRPS type 1 can have full resolution of their symptoms with carpal tunnel release. Future research is needed to understand the pathophysiology and the failures. (J Hand Surg Am. 2025;50(2):130-137. Copyright (c) 2025 by the American Society for Surgery of the Hand. All rights are reserved, including those for text and data mining, AI training, and similar technologies.) Type of study/level of evidence Therapeutic II.