BACKGROUND AND PURPOSE: A clinical-diffusion mismatch (CDM) among stroke patients presenting within 12-24 hours has been correlated with neurologic deterioration and infarct expansion. We sought to study the feasibility and safety of reperfusion therapy in a series of 11 consecutive patients fulfilling this criterion. MATERIALS AND METHODS: Patients presenting with large vessel syndromes were considered for revascularization therapy. Of these patients, we identified those presenting beyond 8 hours who scored ≥8 on the National Institutes of Health Stroke Scale (NIHSS) and had limited abnormalities on diffusion-weighted MR imaging. One- and 7-day NIHSS scores were obtained. Rates of early neurologic deterioration (END, increase in NIHSS score by ≥4 points) and early neurologic improvement (ENI, decrease in NIHSS score by ≥4 points) at 1 week were determined. Follow-up imaging was obtained to evaluate intracranial hemorrhage (ICH). RESULTS: Eleven patients were identified, 8 of whom were successfully revascularized. The mean age of all patients was 55 years with mean initial, 24-hour, and 1-week NIHSS scores of 14 ± 4, 11 ± 7, and 6 ± 5, respectively, with lower scores at 24 hours and 1 week (8 ± 5 and 4 ± 3, respectively) among patients successfully revascularized. Eight of the treated patients (72% of the total, 100% of those successfully revascularized) experienced ENI. No patient had END or ICH. CONCLUSIONS: Endovascular treatment for acute ischemic stroke beyond 8 hours is feasible and may prevent END and promote ENI in patients fulfilling the criteria of a CDM. A prospective study is planned.