Midcarpal instability (MCI) is a cause of chronic wrist pain for which treatment remains controversial. This study's purpose was to determine the outcome of a treatment algorithm for MCI that included immobilization and surgical interventions. We prospectively enrolled 23 consecutive patients (12 males, average age 27 years) with 27 symptomatic wrists. All had generalized wrist pain with an average duration of 22 months. All had MCI and a catch-up clunk that reproduced the symptoms. Initial treatment was full immobilization for 6 weeks. When necessary, recurrence after immobilization was treated with an anatomically based surgical procedure to plicate the dorsal capsule and extrinsic ligaments to stabilize the midcarpal joint. Failure of surgical plication was followed by 4-corner intercarpal arthrodesis when necessary. Patients were observed for instability, grip strength, wrist motion, and Patient-Rated Wrist Evaluation. For 22 wrists there was partial relief of symptoms with full-time cast or orthosis immobilization; however, symptoms quickly returned with mobilization. The other wrists had previously been immobilized and patients refused further nonsurgical care. All patients underwent surgical plication of the dorsum of the wrists. Postoperative follow-up (35 months) showed statistically significant improvements in grip strength and Patient-Rated Wrist Evaluation scores. All patients had improved pain at final follow-up. Most improvement was in female patients aged under 25 years, with hypermobility and without major traumatic or work-related injuries. This contrasted with poorer outcomes in men aged over 25years who had moderate or severe trauma that was mostly work-related. Instability recurred in 2 patients who then had a 4-corner arthrodesis. Immobilization was not successful in controlling pain and recurrence of instability in patients with MCI. Surgical midcarpal capsular plication was less effective in men with posttraumatic instability. The capsular plication procedure was successful in young female patients with ligament laxity and a history of only minor or repetitive trauma and no history of major trauma. Therapeutic IV.