Vessel repair requires the coordinated actions of multiple cell types in order to effect coagulation, inflammation, repair of the injured endothelium, and resolution of inflammation. Using zebrafish embryos, we demonstrate that the dynamics of the thrombus, leukocytes, and the vascular endothelium can be tracked and quantified using real-time microscopy over the entire course of injury repair. This system affords a unique opportunity to study vascular repair in vivo using genetic and pharmacological manipulation. We find that macrophage influx to the wound site is coincident with thrombus dissolution, and that while initial macrophage recruitment is independent of thrombus formation, persistence at the wound site after re-establishment of blood flow requires local fibrin deposition, and macrophages are actively involved in clearance of the thrombus. Depletion of macrophages, but not neutrophils, leads to increased healing times secondary to the increased persistence of the thrombus at the wound site. Taken together, our data demonstrate that thrombus removal is rate-limiting during vascular repair and that macrophages are required during this process.