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Corticosteroid injection is a recommended treatment option for carpal tunnel syndrome, before considering surgery. Nevertheless, injections remain controversial because there is strong evidence of only short-term benefits. This study aimed to determine the reintervention rate and to identify prognostic indicators for subsequent treatment after corticosteroid injection for carpal tunnel syndrome.This study evaluated residents of Olmsted County treated with a corticosteroid injection for carpal tunnel syndrome between 2001 and 2010. Treatment failure was the primary outcome of interest. Two definitions for failure were examined: (1) the patient receiving subsequent procedural intervention and (2) the patient undergoing carpal tunnel release. Survival was estimated using Kaplan-Meier methods, and association of covariates with increased failure was modeled using Cox proportional hazards regression.The study included 774 affected hands in 595 patients. The median follow-up period was 7.4 years. Reintervention was performed in 68 percent of cases, of which 63 percent resulted in eventual surgery. Injectate volume was significant for the outcome of any retreatment [hazard ratio, 0.879 (95 percent CI, 0.804 to 0.96)] and surgery [hazard ratio, 0.906 (95 percent CI, 0.827 to 0.99)]. Rheumatoid arthritis was also significant in both models, with a hazard ratio of 0.627 (95 percent CI, 0.404 to 0.97) for any retreatment and 0.493 (95 percent CI, 0.292 to 0.83) for surgery.In this cohort, 32 percent of patients did not receive subsequent treatment after a single injection, which indicates that there is a therapeutic role for corticosteroid injections in treating carpal tunnel syndrome. Further research is necessary to identify those patients who will benefit from an injection, to provide more individually tailored treatment.Risk, III.