BACKGROUND: Acute lower limb ischemia (ALI) is associated with a high risk of limb loss and death. OBJECTIVE: The present study evaluates the safety of intraoperative, local urokinase lysis in patients with ALI and crural artery occlusion. METHODS: A total of 107 patients (115 legs) were treated surgically for ALI with additional intraoperative urokinase lysis to improve the outflow tract. Minor and major bleeding as well as efficacy of treatment and amputation-free survival were investigated. RESULTS: Complete restoration of at least one run-off vessel was achieved in 64%. Collateralization was improved in 34%. Lysis failed in 2%. Major amputation rate was 27% overall (12% within 30 days) and depended on Rutherford class of ALI (overall/30 day: IIa 11%/6%; IIb 20%/17%; III 37%/15%). Amputation-free survival turned out to be 82% after 30 days, 58% after one, and 41% after five years. Minor bleeding occurred in 21% (24/115) and major bleeding in 3.5% (4/115). One of these patients died of haemorrhage. No patient experienced intracranial bleeding. CONCLUSIONS: Intraoperative urokinase lysis improves limb perfusion and causes low major and intracranial bleeding. It can be safely applied to patients with severe ischaemia when surgical restoration of the outflow tract fails.