The Penumbra Stroke System (PSS) was cleared for use in patients with ischemic stroke by the FDA in January 2008. We describe our experience of using this new system in acute large vessel occlusive disease following thrombolysis. Fifteen consecutive patients (mean age 60 years) suffering from acute ischemic stroke were treated with the PSS after intravenous or intra-arterial standard treatment with tissue plasminogen activator (n = 14) or ReoPro (n = 1). All patients presented with TIMI 3 before use of the PSS. Carotid stenting (n = 3) and intracranial balloon angioplasty or stenting (n = 2) were performed if indicated. Neurological evaluation was performed using the NIHSS score and the mRS score. Initial median NIHSS score in 12 patients with occlusions in the anterior circulation was 15; three patients with basilar artery occlusion presented with coma. Median symptom to procedure start time was 151 min. In the anterior circulation, 9 of the 12 target vessels were recanalised successfully (TIMI 2 and 3). The rate of patients with independent clinical outcome (mRS </= 2) was 42%. One patient died 5 days after unsuccessful treatment, one after 28 days and one after 85 days owing to heart attack. Basilar artery occlusions could be recanalised in all cases to TIMI 3. The clinical result after 90 days was mRS 4 in two cases and mRS 5 in one case. Symptomatic haemorrhage did not occur. The PSS can safely be used for recanalisation in patients with acute ischemic stroke due to large vessel occlusion, who have already received thrombolysis treatment. The recanalisation rate was 80%. Symptomatic haemorrhage did not occur. Randomized trials may demonstrate that endovascular mechanical thrombectomy improves patient outcome.