It is unknown whether collateral vessel status, as seen on computed tomography angiography, can predict the fate of penumbral tissue identified on perfusion computed tomography and thereby influence clinical outcome. We tested this hypothesis in consecutive patients who underwent perfusion computed tomography/computed tomography angiography within 6 h of anterior circulation stroke, who also had repeat perfusion/infarct volume imaging at 24 h, and modified Rankin Scale at 3 months. Collateral status was graded as good or reduced depending on the extent of contrast visualized distal to the occlusion on computed tomography angiography. 'Perfusion computed tomography mismatch' ratio was calculated from the ratio of the mean transit time lesion/cerebral blood volume lesion. Of 92 patients with proximal intracranial vessel occlusion, good collateral status (51/92) was significantly associated with reduced infarct expansion and more favourable functional outcomes (modified Rankin Scale 0-2). Significant univariate predictors of favourable outcome were good collateral status, major reperfusion at 24 h, presence of perfusion computed tomography mismatch (for a range of ratios: > or = 1.2, > or = 2, > or = 3, > or = 3.5) and baseline National Institutes of Health Stroke Scale score. Notably, none of the 37 patients with a perfusion computed tomography mismatch ratio < 3.0 had a favourable outcome. In patients with perfusion computed tomography mismatch, significant independent predictors of favourable outcome were good collateral status, major reperfusion and baseline National Institutes of Health Stroke Scale score. There was also a strong interaction between major reperfusion and good collateral status in the regression models. In patients with proximal vessel occlusion, perfusion computed tomography mismatch is a prerequisite for a favourable clinical response, but good collateral status appears a critical determinant of ultimate outcome, particularly if major reperfusion occurs.