OBJECTIVE To compare responsiveness based on item response theory (IRT) with that based on conventional scoring for two patient-reported outcomes measures in carpal tunnel syndrome (CTS); the short disabilities of the arm, shoulder, and hand (QuickDASH) measure, and the 6-item CTS symptoms scale (CTS-6). STUDY DESIGN AND SETTING Prospective cohort study of patients with CTS undergoing carpal tunnel release at one orthopedic department. Of 455 consecutive patients, 343 completed the QuickDASH and the CTS-6 before and within 1 year after surgery. IRT-based and conventional scores were compared in subgroups according to global rating of change in hand status and treatment satisfaction. The effect size (ES) and the area under the receiver operating characteristic (ROC) curve were used as measures of responsiveness. RESULTS The mean value for the IRT-based QuickDASH estimate was -0.09 (standard deviation [SD]=1.13) preoperatively and -2.14 (SD=1.79) postoperatively (ES=-1.8) and for the CTS-6 estimate was 0.29 (SD=1.36) preoperatively and -3.87 (SD=2.3) postoperatively (ES=-3.1), indicating very large improvement. The ES for the QuickDASH and CTS-6 were very large (-2.4 and -3.8), respectively, in the group with the largest perceived improvement and decreased with lower perceived improvement. The ES was consistently larger with IRT-based scoring than conventional scoring. The AUC for the QuickDASH and CTS-6 exceeded 0.85. CONCLUSION IRT-based scoring showed high responsiveness for the QuickDASH and CTS-6, and the ES were larger than those estimated using conventional scoring.