A randomized single-blind cohort study of 186 patients was conducted to determine whether the subjective complaint of swelling of the hand or wrist is associated with the diagnosis and/or prognosis of carpal tunnel syndrome. All patients were referred for splinting with a presenting clinical diagnosis of carpal tunnel syndrome from outpatient specialty clinics, including orthopedics, rheumatology, and neurology. Patients were assessed before splinting for the complaint of subjective swelling and underwent a clinical examination including Phalen testing and carpal compression testing. In addition, 211 of the 290 joints underwent electrodiagnostic testing by the end of this study. Two weeks after splinting, an assessment was made of the subjective response to splinting. Chi2 analysis was then performed to assess the correlation among the Phalen test, carpal compression test, and nerve conduction study results and the symptom of subjective swelling at presentation with that of response to splinting. Subjective swelling of the hand showed a trend toward association with electrodiagnostic results (although this finding was not statistically significant) and proved to be significantly correlated with a poor clinical response to splinting. Positive electrodiagnostic findings were significantly, though positively, correlated with pain relief from splinting. This study, therefore, introduces the complaint of subjective swelling of the affected hand as an important diagnostic and prognostic symptom for the assessment and treatment of carpal tunnel syndrome.