Surgical revascularization as the initial therapy in acute lower limb ischemia (ALLI) is associated with a high cumulative mortality and amputation rate. Catheter-directed delivery of low-dose thrombolytic agents (intra-arterial thrombolysis, IAT) offers the possibility for a gentle revascularization with a minimum of stress for the patients. In two randomized studies, the primary rates of revascularization, amputation, and mortality did not differ significantly between IAT and surgical revascularization. However, in one study the 6-month event-free survival rate was 85% in the IAT group, and 63% in the surgical group. Also in the second study the 12-month results were significantly better in the IAT group (event-free survival 75%) than in the surgical group (event free survival 52%). The high-dose urokinase regimen recommended by some authors in IAT is associated with an unacceptable cerebral bleeding rate of up to 2%. Low-dose recombinant tissue-type plasminogen activator (rt-PA) (0.02 to 0.05 mg/h) is the most suitable agent in IAT because of rapid lysis and low bleeding complications. Patients with ALLI, classified as viable or threatened without neurologic deficit, benefit most from the IAT as the initial therapy in ALLI. When IAT is performed as the initial therapy in ALLI, surgical intervention becomes unnecessary in approximately one-third of the patients. In another third the subsequent correction of the cause of the ALLI can be performed electively, which reduces mortality and morbidity rates.