Background: The modified and original variants of the TICI scale (mTICI and oTICI) define substantial reperfusion in endovascular stroke therapy (EVT) as ≥50% (mTICI) or ≥67% (oTICI) of the downstream territory. Despite recent adoption of the mTICI definition, it remains uncertain which threshold better predicts good clinical outcome after EVT. Methods: The angiography core lab of the IMS III trial evaluated use of the oTICI definition compared to the mTICI technical endpoint. Inclusion criteria were presence of an intracranial ICA or MCA M1 occlusion, active EVT and available 90-day mRS. Two expert readers independently reviewed the complete angiography studies to categorize mTICI 2B results into 50-66% vs. 67-99% reperfusion and differences were resolved by consensus. ROC analysis was performed to determine the optimal threshold for predicting good clinical outcome (mRS 0-2). Safety endpoints were mortality and symptomatic intracranial hemorrhage. Inter-rater agreement was assessed using the kappa statistic. Results: 187 patients met inclusion criteria with mean age 65.7 years and median NIHSS 19 were included, with 56 ICA and 131 M1 occlusions. The mTICI was 0 in 32 patients, 1 in 17, 2A in 69, 2B in 64, and 3 in only 5. Of the 64 mTICI 2B cases, 38 (59%) were adjudicated as oTICI 2B (i.e., 67-99%). There was an increase in good outcomes with greater reperfusion (mTICI 2B, 46%; oTICI 2B, 53%; p<0.0001), although there was no significant pairwise difference between 50-66% vs. 67-99% (p=0.80). For good outcome, the c-statistic was non-significantly higher for mTICI vs. oTICI (0.76 vs. 0.73, p=0.19). Overall, the optimal threshold for predicting good outcome was mTICI 2B-3 (sensitivity 68%, specificity 75% vs. sensitivity 45%, specificity 86% for oTICI 2B-3). Similarly, mTICI 2B-3 was the optimal threshold for predicting decreased mortality and decreased sICH. Inter-rater agreement for discriminating 50-66% vs. 67-99% reperfusion was excellent (kappa=0.84). Conclusions: Greater degrees of reperfusion are associated with a higher likelihood of good outcomes. The most effective threshold, however, for predicting both good clinical outcome and improved safety is mTICI 2B rather than oTICI 2B.