PURPOSE: The phenomenon of futile recanalization, defined as lack of clinical benefit despite angiographic recanalization, is an important limitation of endovascular treatment for acute ischemic stroke. We aim to characterize the occurrence and predictors of futile recanalization in the endovascular arm of the Interventional Management of Stroke (IMS) III trial. METHODS: Patients with near complete or complete recanalization (TICI grades 2b and 3) were divided according to functional outcome at 3 months into "meaningful recanalization," defined as mRS score 0-2, and "futile recanalization," mRS score 3-6. Multivariate analysis was performed to identify predictors of futile recanalization. RESULTS: Futile recanalization was observed in 61 (47%) of 130. Compared to meaningful recanalization group, the futile recanalization group had higher proportion of women (62.3 vs. 43.5%; p = 0.032), higher incidence of diabetes mellitus (29.5 vs. 8.7%; p = 0.004) and coronary artery disease (27.9 vs. 13%; p = 0.05), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (median [range] 19 [11-31] vs. 15 [8-26], p < 0.001), higher baseline serum glucose (7.6 +/- 2.6 vs. 6.7 +/- 1.7 mmol/L; p = 0.039), and longer onset-to-start of endovascular treatment time (265.8 +/- 48.3 vs. 239.2 +/- 47.7 min; p = 0.007). In multivariate analysis, NIHSS (OR 1.3; 95% CI 1.1-1.4), female gender (OR 3.0; 95% CI 1.1-8.2), and onset-to-start of endovascular treatment time (OR 1.2; 95% CI 1.1-1.3) were independent predictors of futile recanalization. CONCLUSION: In IMS III, futile recanalization was common. Delay in endovascular treatment is the only modifiable risk factor. Additional strategies for non-modifiable risk factors-female gender and high NIHSS-need to be identified.