Arterial reocclusion has not been systematically studied despite the fact that 13% of patients in the National Institute of Neurological Diseases and Stroke rt-PA Trial deteriorated following initial improvement, suggesting that reocclusion might be responsible for poor clinical outcome in some of these patients. Consecutive stroke patients treated with IV tissue plasminogen activator (TPA) within 3 hours and an M1 or M2 middle cerebral artery (MCA) occlusion on pre-TPA transcranial Doppler (TCD) were monitored up to 2 hours after TPA bolus. Reocclusion was defined as the Thrombolysis in Brain Ischemia flow decrease by >/=1 grades and no hemorrhage on repeat CT. The NIH Stroke Scale (NIHSS) and modified Rankin Scores (mRS) were obtained by a neurologist independently of TCD. Sixty patients with median prebolus NIHSS score of 16 (range 6 to 28, 90% with >/=10 points) had TPA bolus at 130 +/- 32 minutes (median 120 minutes, 58% within the first 2 hours). Recanalization was complete in 18 (30%), partial in 29 (48%), and none in 13 (22%) patients. Reocclusion occurred in 34% of patients with any initial recanalization (16/47): in 4 of 16 patients with complete recanalization (22%), and in 12 of 29 patients with partial recanalization (41%). Reocclusion was detected in four patients (25%) before TPA bolus, in three (19%) by 30 minutes after bolus, in three (19%) by the end of infusion, and in six (37%) by 60 to 120 minutes. Before reocclusion, those patients had earlier median timing of recanalization: 130 versus 180 minutes after stroke onset compared with those who recanalized without reocclusion (p = 0.01). Median prebolus NIHSS score in the reocclusion group was 13.5 versus 17 (rest, NS), whereas at 2 and 24 hours, their NIHSS scores were higher: 14 versus 9 and 16 versus 6 points (p /=4 NIHSS points occurred in 8 of 16 (50%) patients with reocclusion versus 10% (rest) (p < 0.05). In-hospital mortality was 25 versus 3% (p < 0.0001). At 3 months, good outcome (mRS score of 0 to 1) was achieved by 8% of patients with no recanalization, by 33% of patients with reocclusion, and by 50% of patients with stable recanalization (p