Rhabdomyolysis (RHAB) is a known complication following blunt trauma. RHAB after penetrating trauma has not been studied. The objective of this study was to evaluate the incidence, risk factors, and complications of RHAB following penetrating trauma. Over a 5-year period, penetrating trauma patients admitted to our intensive care unit (ICU) were studied. Significant RHAB was defined as a CK level of 5000 U/L or higher. There were 873 patients (29 +/- 12 years old, 92% male), of whom 767 (88%) had abnormal CK levels (range 520-165,943 U/L), and 111 patients (13%) developed significant RHAB. Victims of penetrating trauma who sustain vascular and severe extremity injury are at a sixfold increased risk to develop significant RHAB. Patients with significant RHAB had a higher rate of renal failure (23% vs 7%, P < 0.0001) and longer ICU stay (15 +/- 26 days vs 8 +/- 12 days, P < 0.0001). CK elevations and significant RHAB are common after penetrating trauma. Patients who sustain vascular and severe extremity injury as a result of their penetrating wounds are at high risk to develop significant RHAB, resulting in renal failure and prolonged ICU stay. Therefore, critically injured penetrating trauma patients should be routinely screened with CK levels.