8 Background: Late secondary injury following vessel recanalization, recently observed in animal stroke models, may limit the benefit of reperfusion therapy. The frequency and clinical correlates of secondary injury in humans have not been previously characterized. Methods: Diffusion-perfusion MRIs were performed prior to treatment, early after recanalization (median 4 hrs), and at day 7 in patients undergoing vessel recanalization with intra-arterial (IA) thrombolytics. Post-treatment MRIs were co-registered to the pretreatment scan to allow a voxel-by-voxel analysis of tissue fate over time. Results: Eighteen patients (13 females, 5 males) were studied. Mean age was 71 and median entry NIHSS score 13. Early after recanalization, partial or complete normalization of DWI abnormalities occurred in 8/18 (44%) patients, and of apparent diffusion coefficient (ADC) abnormalities in 13/18 (72%). Among the 8 patients with early DWI reversal, late secondary injury on day 7 (on DWI or T2W sequences) occurred in 5 (63%), and sustained normalization of all reversed tissue in 3 (38%). Across all patients, of tissues showing pretreatment DWI abnormality, 41% of voxels showed no early reversal, 33% early reversal with sustained normalization at day 7, and 18% early reversal but late secondary injury. Pretreatment ADC values were lowest in regions experiencing no reversal (mean ADC 624 um2/sec), intermediate in regions with reversal and secondary decline (641), and highest in regions with sustained reversal (677). Evolution of neurologic deficit (NIHSS) did not differ in patients with secondary injury vs. those with sustained reversal, nor did age, time to recanalization, degree of recanalization, or presence of post-ischemic hyperperfusion. Conclusions: Following vessel recanalization with IA thrombolysis, partial or complete reversal of initial DWI abnormality occurs in ∼40% of patients. A late, secondary signature of injury compromising some or all of the initially normalized tissue occurs in over 50% of these patients, but is not associated with clinical worsening.