Intra-arterial thrombolysis has become the most important minimally-invasive treatment option to treat acute lower limb ischemia. Although hemorrhagic stroke is a dreaded complication, intra-arterial thrombolysis is considered beneficial to many fragile and elderly patients where vascular surgery is not an option. This review outlines current results after intra-arterial thrombolysis with low dose recombinant tissue plasminogen activator (rtPA) from 2001 to 2012 in two large vascular centers in Sweden. There was an increasing number of thrombolysis of occluded endoprosthesis and decreasing thrombolysis of occluded bypasses during this time period. Technical success rate for thrombolysis of occluded endoprostheses, bypasses and native artery occlusion was 91%, 89% and 73%, respectively. Amputation-free survival rate at one year was 73%. Popliteal arterial aneurysm and anemia were independently associated with dismal amputation-free survival at 30 days. Independent factors associated with dismal amputation-free survival at long-term were foot ulcers, motor deficit, renal insufficiency and anemia. Major hemorrhage occurred in 104 procedures (13.9%); 43 (5.7%) were so severe that thrombolysis was discontinued in advance. All three (0.4%) hemorrhagic strokes were fatal. Preoperative severe limb ischemia with motor deficit was the only independent risk factor for major bleeding. Simultaneous heparin infusion was not associated with increased risk of major bleeding or improved leg salvage or survival. In conclusion, intra-arterial thrombolysis with rtPA for lower limb ischemia was effective, with few major bleeding complications. Simultaneous heparin infusion offered no advantage. Thrombolysis in embolism due to popliteal artery aneurysm is the most important step to improve run-off and a prerequisite to succeed with operative treatment.