Background: The aim of this study was to investigate the presence, etiology and clinical significance of elevated troponin I in patients with acute upper or lower limb ischemia. The high sensitivity and specificity of cardiac troponin for the diagnosis of myocardial cell damage suggested a significant role for troponin in the patients investigated for this condition. The initial enthusiasm for the diagnostic potential of troponin was limited by the discovery that elevated cardiac troponin levels are also observed in conditions other than acute myocardial infarction, even conditions without obvious cardiac involvement. Patients and Methods: 71 consecutive patients participated in this study. 31 (44%) of them were men and mean age was 75.4 ± 10.3 years (range 44–92 years). 60 (85%) patients had acute lower limb ischemia and the remaining (11; 15%) had acute upper limb ischemia. Serial creatine kinase (CK), isoenzyme MB (CK-MB) and troponin I measurements were performed in all patients. Results: 33 (46%) patients had elevated peak troponin I (> 0.2 ng/ml) levels, all from the lower limb ischemia group (33/60 vs. 0/11 from the acute upper limb ischemia group; p = 0.04). Patients with lower limb ischemia had higher peak troponin I values than patients with upper limb ischemia (0.97 ± 2.3 [range 0.01–12.1] ng/ml vs. 0.04 ± 0.04 [0.01–0.14] ng/ml respectively; p = 0.003), higher peak CK values (2504 ± 7409 [range 42–45 940] U/ml vs. 340 ± 775 [range 34–2403] U/ml, p = 0.002, respectively, in the two groups) and peak CK-MB values (59.4 ± 84.5 [range 12–480] U/ml vs. 21.2 ± 9.1 [range 12–39] U/ml, respectively, in the two groups; p = 0.04). Peak cardiac troponin I levels were correlated with peak CK and CK-MB values. Conclusions: Patients with lower limb ischemia often have elevated troponin I without a primary cardiac source; this was not observed in patients presenting with acute upper limb ischemia. It is very important for these critically ill patients to focus on the main problem of acute limb ischemia and to attempt to treat the patient rather than the troponin elevation per se. Cardiac troponin elevation should not prevent physicians from providing immediate treatment for limb ischaemia to these patients, espescially when signs, symptoms and electrocardiographic findings preclude acute cardiac involvement.