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Supplemental Digital Content is Available in the Text. Objective: To assess initial and mid-term efficacy of botulinum toxin A (BoNT-A) injections in patients with chronic exertional compartment syndrome (CECS) in the lower and upper limbs. Design: Retrospective monocentric study. Setting: A University Hospital Department of Physical Medicine and Rehabilitation. Patients: Sixteen patients with CECS of the lower and upper limbs treated with BoNT-A injections (first-line treatment) were included. Interventions, Main Outcome Measures: We collected data from a follow-up consultation (initial pain reduction [complete, partial, or ineffective] and specific activities triggering CECS) and a subsequent phone questionnaire (mid-term efficacy, pain recurrence, and adverse effects). Results: Sixteen patients were included (median age: 25.5 years), and 68.75% reported initial efficacy (4 partial and 7 complete); 8/16 patients were able to resume the activity that triggered CECS. All the patients with initial partial efficacy had pain recurrence (median time of 2.25 months). Among patients with initial complete efficacy, 57.14% had recurrence (median time of 5 months). Minor adverse effects were observed, but with no functional impact. Conclusion: In 16 individuals with CECS treated with BoNT-A injections, we observed moderate efficacy without major adverse effects, but an initial improvement was often followed by recurrence, especially among those with partial initial efficacy. [ABSTRACT FROM AUTHOR]