The reconstruction of complex defects using free microsurgical flaps is an integral part of modern plastic and reconstructive surgery. Despite success rates of over 95%, flap loss is associated with considerable aesthetic and functional limitations for those affected and often requires multiple reoperations. Against this background, optimizing the safety of free flaps is of immense clinical importance. This animal experiment project investigates the effectiveness of intra-arterial or intravenous thrombolysis in arterial and venous thrombosis of free flaps—both fasciocutaneous and muscular types. Based on the results, an evidence-based treatment algorithm for the use of thrombolytic substances in clinical practice will be developed.