Background and Purpose-Both intraventricular fibrinolysis (IVF) and lumbar drainage (LD) may reduce the need for exchange of external ventricular drainage (EVD) and shunt surgery in patients with intracerebral hemorrhage and severe intraventricular hemorrhage. We investigated the feasibility and safety of IVF followed by early LD for the treatment of posthemorrhagic hydrocephalus. Methods-This prospective study included patients with spontaneous ganglionic intracerebral hemorrhage and severe intraventricular hemorrhage with acute obstructive posthemorrhagic hydrocephalus who received an EVD (nϭ32). The treatment algorithm started with IVF (4 mg recombinant tissue plasminogen activator every 12 hours) until clearance of the third and fourth ventricles from blood. Thereupon, EVD was clamped and if clamping was unsuccessful, communicating posthemorrhagic hydrocephalus was assumed and LD placed. EVD was removed if there was neither an increase of intracranial pressure nor ventricle enlargement on CT. A ventriculoperitoneal shunt was indicated if "LD weaning" was unsuccessful for Ͼ10 days. Outcome was assessed at 90 and 180 days using the modified Rankin Scale. Results-IVF resulted in fast clearance of the third and fourth ventricles (73Ϯ50 hours). However, early EVD removal was only possible in 4 patients. The remaining 28 patients developed communicating posthemorrhagic hydrocephalus. In all of these patients, early LD was capable to replace EVD. EVD exchange was not necessary and EVD duration was 105Ϯ59 hours. Only one patient required a ventriculoperitoneal shunt. At 180 days, 20 (62.5%) patients had a good (modified Rankin Scale 0 to 3) outcome and 5 (15.6%) patients had died. One patient had asymptomatic ventricular rebleeding. Conclusions-In patients with secondary intraventricular hemorrhage and posthemorrhagic hydrocephalus, the combined treatment approach of IVF and early LD is safe and feasible, avoids EVD exchange, and may markedly reduce the need for shunt surgery.