A high‐power prototype dedicated to trans‐skull therapy has been tested invivo on 20 sheep. The array is made of 200 high‐power transducers working at 1‐MHz central and is able to reach 260 bars at focus in water. An echographic array connected to a Philips HDI 1000 system has been inserted in the therapeutic array in order to perform real‐time monitoring of the treatment. A complete craniotomy has been performed on half of the treated animal models in order to get a reference model. On the other animals, a minimally invasive surgery has been performed thanks to a time‐reversal experiment: a hydrophone was inserted at the target inside the brain thanks to a 1‐mm2 craniotomy. A time‐reversal experiment was then conducted through the skull bone with the therapeutic array to treat the targeted point. For all the animals a specified region around the target was treated thanks to electronic beam steering. Animals were finally divided into three groups and sacrificed, respectively, 0, 1, and 2 weeks after treatment. Finally, histological examination confirmed tissue damage. These invivo experiments highlight the strong potential of high‐power time‐reversal technology.