The aim of the study was to determine the effect of comorbidity conditions on the early outcome and complication rates of thrombolytic treatment of lower limb ischaemia with recombinant tissue plasminogen activator (rt-PA). Clinical and procedural data of 82 patients treated for acute/subacute arterial/graft occlusion were analysed retrospectively. Early results and adverse events were recorded and evaluated statistically. Early resolution of ischemic symptoms was achieved in 67 (82%) patients with a median dose of 25.4 mg of rt-PA. Major bleeding was reported in 9 and minor bleeding in 6 cases (intracranial hemorrhage rate 1%, mortality rate 1%, major amputation rate 1%). Comorbidity conditions and patient characteristics did not statistically influence success and complication rates. Bleeding was observed in patients who received a higher dose of the thrombolytic agent (30.0 mg vs 24.3 mg). Comorbidity conditions have no effect on early outcome and adverse events after thrombolytic management of lower limb ischemia. Higher doses of rt-PA with prolonged infusion times increase the risk of occurrence of treatment-related bleeding.