Abstract Background Acute ischemic stroke (AIS) is a common neurological event that causes varying degrees of disability. AIS outcome varies considerably, from complete recovery to complete loss of tissue and function. This diversity is partly explained by the compensatory ability of the collateral circulation and the ensuing cerebral flow grade. The collateral flow to the anterior circulation largely supplies the cortical areas. The deep brain tissue is supplied by penetrating arteries and has little or no collateral supply. Although these brain compartments differ substantially in their collateral supply, there are no published data on the different effects the collateral circulation has on them. In addition, the influence of baseline collateral flow on the final infarct size following endovascular or reperfusion therapies remains unknown. This study was designed to determine the effect of the collateral circulation on cortical infarct volume and deep infarct volume, and to investigate the relation between the collateral grade, response to reperfusion therapy and clinical outcome. Methods We studied consecutive patients presenting to our medical center between April 2008 and April 2012 with AIS and anterior proximal artery occlusion. To be included patients had to undergo a computerized tomographic angiographic study within 12 h of symptom onset demonstrating the occlusion. Imaging data and clinical and laboratory values were extracted retrospectively from the original scans and medical records. Cortical infarct volume (CIV) and deep infarct volume (DIV) were calculated as well as collateral grade. Clinical outcome was assessed at discharge using the modified Rankin Scale (mRS). Results Of the 51 study patients, 13 were treated conservatively, 22 received intravenous recombinant tissue plasminogen activator, and 16 received intra-arterial thrombolysis. The collateral grading was similar for all three treatment groups. While there was a moderate inverse correlation between the collateral grade and CIV (Spearman’s rho = −0.49, P