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Identifying the severity of carpal tunnel syndrome (CTS) is essential to providing appropriate therapeutic interventions. We developed and validated machine-learning (ML) models for classifying CTS severity. Here, 1037 CTS hands with 11 variables each were retrospectively analyzed. CTS was confirmed using electrodiagnosis, and its severity was classified into three grades: mild, moderate, and severe. The dataset was randomly split into a training (70%) and test (30%) set. A total of 507 mild, 276 moderate, and 254 severe CTS hands were included. Extreme gradient boosting (XGB) showed the highest external validation accuracy in the multi-class classification at 76.6% (95% confidence interval [CI] 71.2–81.5). XGB also had an optimal model training accuracy of 76.1%. Random forest (RF) and k-nearest neighbors had the second-highest external validation accuracy of 75.6% (95% CI 70.0–80.5). For the RF and XGB models, the numeric rating scale of pain was the most important variable, and body mass index was the second most important. The one-versus-rest classification yielded improved external validation accuracies for each severity grade compared with the multi-class classification (mild, 83.6%; moderate, 78.8%; severe, 90.9%). The CTS severity classification based on the ML model was validated and is readily applicable to aiding clinical evaluations. [ABSTRACT FROM AUTHOR]