OBJECTIVE : Uncertainty exists about what change in Patient-Reported Outcomes Measurement Information System (PROMIS) scores represents a clinically relevant improvement (minimal clinically important difference [MCID]) in hand surgery care. Using a region-specific patient-reported outcome measure (PROM) (Michigan Hand Question [MHQ]) and a condition-specific PROM (Boston Carpal Tunnel Questionnaire [BCTQ]), MCID values were determined for PROMIS Physical Function (PF), Upper Extremity (UE), and Pain Interference (PI) computerized adaptive testing among patients undergoing carpal tunnel release (CTR). METHODS : Patients undergoing CTR with a single surgeon from November 2014 to April 2017 were asked to complete the BCTQ, MHQ, and PROMIS PF, UE, and PI at each visit. Patients who had completed questionnaires both at a preoperative and either a 6-week or a 3-month postoperative visit were included. The PROMIS PF, UE, and PI MCID values were calculated using previously determined MCID estimates in the literature with both region- (ie, MHQ) and condition-specific (ie, BCTQ) PROM anchors. The PROMIS domain MCID estimates were also determined using the distribution-based method. RESULTS : A total of 70 patients fit our inclusion criteria. Using MHQ Function and Pain, PROMIS UE, PF, and PI MCIDs were 6.3, 1.8, and -8.9, respectively. Using the average of the 2 BCTQ domains, PROMIS UE, PF, and PI MCIDs were 8.0, 2.8, and -9.7, respectively. Using the distribution-based method, PROMIS UE, PF, and PI MCIDs were 4.2, 2.7, and -4.1, respectively. CONCLUSIONS : Using region- and condition-specific PROMs, we were able to provide MCID estimates of PROMIS UE, PF, and PI for patients undergoing CTR. CONCLUSIONS : Estimating PROMIS UE, PF, and PI MCIDs in CTR using validated region- and condition-specific PROMs provides hand surgeons a way to evaluate CTR outcomes not previously described in the literature. Surgeons should understand that these values are only estimates and future work is needed to verify whether they reflect clinical improvement.