Objectives: CT angiography (CTA) is recommended as a standard of stroke imaging. We investigated accuracy and precision of standard or single-phase CTA as compared with novel technique or multiphase CTA in clot detection in the middle cerebral artery. Methods: Twenty single-phase CTA and twenty multiphase CTA with prevailing M2 occlusion were assessed by 10 radiologists and 10 neurologists blinded to clinical information (7 less experienced and 3 experienced). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated as compared with reading by two seniors. Reliability was calculated using Krippendorff's alpha (K-alpha). Results: Sensitivity, specificity, PPV, and NPV of single-phase CTA compared with multiphase CTA for M2 clot presence were, respectively, .86, .75, .90, and .67 versus .88, .82, .92, and .72. For secondary or distal clots, sensitivity, specificity, PPV, and NPV of single-phase CTA compared with multiphase CTA were .41, .83, .50, and .78 versus .65, .77, .71, and .67. Agreement increased significantly in favor of multiphase CTA for detection of primary clots from moderate (.43) to substantial (.65) in less experienced radiologists and from slight (.10) to moderate (.30) in less experienced neurologists. Agreement significantly increased for distal or secondary clot detection in favor of multiphase CTA from fair (.24) to moderate (.49) in experienced radiologists and from slight (.12) to moderate (.46) in experienced neurologists. Conclusions: Multiphase CTA is a reliable imaging tool in M2 clot detection and might represent a beneficial imaging tool in clot detection for less experienced physicians.