T2*-weighted magnetic resonance imaging (MRI) has been reported to help improve detection of intracranial hemorrhage and is widely used in human neuroimaging. To assess the utility of this technique in small animals, interpretations based on this sequence were compared with those based on paired T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences in 200 dogs and cats that underwent brain MRI for suspected intracranial disease. Two sets of images (T2 + FLAIR and T2*) were reviewed separately in random order unaccompanied by patient information and were interpreted as normal or abnormal based on whether intracranial abnormalities were seen. The number and location of intracranial lesions were recorded. Eighty-five studies were considered normal and 88 were considered abnormal based on both sets of images, with good agreement (κ = 0.731) between the two. Susceptibility artifact was present in 33 cases (16.5%) on T2*-weighted images. In 12 cases (6%) a total of 69 lesions were seen on T2*-weighted images that were not seen on T2/FLAIR, all of which were associated with susceptibility artifact caused by presumed intracranial hemorrhage. Pseudolesions were seen on T2*-weighted images in five cases, none of which were associated with susceptibility artifact. Abnormalities were seen on T2/FLAIR images that were not seen on T2*-weighted images in 35 cases, confirming that T2* does not replace standard spin echo sequences. These results support inclusion of T2*-weighted sequences in small animal brain MRI studies and indicate that that a large number of abnormalities (especially hemorrhagic lesions) can go undetected if it is not performed.