Exercise-induced acute compartment syndrome of the thigh is an uncommon entity. We present a rare case of bilateral exercise-induced three-compartment syndrome of the thighs that required fasciotomies. The objective of this study was to understand the history, physical examination, signs, symptoms, pathophysiology, diagnosis, and treatment of compartment syndrome and rhabdomyolysis. A 42-year-old man presented to the Emergency Department (ED) complaining of worsening pain and swelling in both thighs 45 h after performing a lower extremity exercise regimen. The patient's thighs were tender and swollen, but there was no ecchymosis or evidence of trauma. Admitting serum creatinine kinase (CK) was 106,289 U/L. Treatment for rhabdomyolysis was initiated. The next day, he complained of escalating bilateral thigh pain. Repeat serum CK was 346,580 U/L. The patient was diagnosed with bilateral thigh compartment syndrome and immediately taken to the operating room for fasciotomies. Postoperatively, the patient's symptoms improved rapidly and his serum CK quickly returned to normal. His incisions were closed and he returned to normal activities of daily living. Because exercise-induced compartment syndrome is an extremely rare diagnosis with a high risk of poor outcome, this article serves to emphasize the importance of considering this diagnosis during the work-up of patients presenting to the ED with rhabdomyolysis. © 2010 Elsevier Inc.