Purpose <p>Synchronous measures of head kinematics and in vivo brain deformation during rapid head rotation are needed to advance understanding of traumatic brain injury (TBI) mechanics and enhance computational modeling as a tool for injury risk assessment and prevention. The aims of this study were to produce repeatable rapid rotation of the in vivo sheep head, to assess the viability of the sonomicrometry method for measuring multipoint brain displacement, and to quantify the in vivo brain deformation response to rapid rotation.</p> Methods <p>In three anaesthetized adult sheep, arrays of sonomicrometry transceivers were implanted into the brain and rigidly attached to the inner skull surface. Repeatable, rapid, sagittal plane head rotation (nominally about the second cervical vertebra) was induced with a non-impact head rotation apparatus. Computed tomography imaging was performed to assess relative motion between transceivers and brain tissue. Three-dimensional brain displacement, strain, and head kinematics were assessed for repeatability.</p> Results <p>The location of up to 13 (mean = 11) brain transceivers were tracked in each of 11 rapid head rotation tests. Peak head angular acceleration and velocity were up to 38.56 krad/s² and 30.43&#xa0;rad/s, respectively, and average duration of head motion was 241.9 ± 23.1&#xa0;ms. Pre-to-post-test transceiver displacement in brain tissue was less than the spatial resolution of the measurement system, and brain displacements measured during rapid head rotation had excellent repeatability (CORA score 0.99). Brain displacements and strains up to 2.47&#xa0;mm and 18%, respectively, were observed. The brain exhibited decaying sinusoidal rotational deformation in the sagittal plane with oscillating tension-compression waves.</p> Conclusion <p>Sonomicrometry was reliably applied in vivo and provided repeatable measurements of brain deformation in a non-survival large animal model of rapid head rotation.</p>