The causes of persistent wrist pain following carpal tunnel release include scar tenderness and pillar pain. The goal of this study was to evaluate latent pisotriquetral arthrosis as a source of ulnar-sided wrist pain following open carpal tunnel release. Seven hundred consecutive carpal tunnel releases were reviewed, looking for postoperative presentation of pisotriquetral arthrosis, as well as management and outcome. Fourteen patients with long-standing postoperative pain at the base of the hypothenar eminence had clinical and radiographic signs of pisotriquetral degenerative arthrosis, which conceivably had existed preoperatively and been unmasked thereafter. In 6 patients with persistent symptoms despite conservative measures, excision of pisiform was curative. Altered isometric stresses over the pisotriquetral articulation as a result of releasing the transverse ligament, which constitutes a major radial static stabilizer of this joint, seems to cause articular maltracking, and consequently aggravates a preexisting asymptomatic pisotriquetral arthrosis. Long-standing discomfort is characteristically associated with loss of grip strength and dexterity. Pisotriquetral dysfunction and arthrosis should always be considered in the differential diagnosis of persistent wrist pain following either open or endoscopic carpal tunnel release that does not respond to nonoperative measures. Clinical scrutiny, adequate clinical inspection, and radiographic evaluation readily establish the diagnosis. Conservative treatment includes immobilization, nonsteroidal anti-inflammatory drugs, and intra-articular injection of corticosteroids under fluoroscopic control. The corticosteroid injection combined with a local anesthetic also serves as a diagnostic test. Excision of the pisiform is indicated where conservative treatment has failed.