Paradoxical brain herniation (PBH) is a rare and potentially life-threatening complication of decompressive craniectomy (DC) and results from the combined effects of brain gravity, atmospheric pressure and intracranial hypotension causing herniation in the direction opposite to the site of the DC with subsequent brainstem compression. To date, the cases of PBH reported in literature are spontaneous or provoked by a lumbar puncture, a cerebrospinal fluid (CSF) shunt, or ventriculostomy.We present an uncommon case of PBH provoked by percutaneous drainage of a huge subdural hygroma (SH) ipsilateral to the decompressive craniectomy causing mass effect and neurologic deterioration. After percutaneous evacuation of SH, the patient became unresponsive with dilated and fixed left pupil. A brain computed tomography scan showed marked midline shift in the direction opposite to the craniectomy site with subfalcine herniation and effacement of the peripontine cisterns. Paradoxical brain herniation (PBH) was diagnosed. Conservative treatment failed, and the patient required an emergency cranioplasty for reverse PBH.The present case highlights the possibility that all forms of CSF depletion, including percutaneous drainage of subdural CSF collection and not only CSF shunting and/or lumbar puncture, can be dangerous for patients with large craniotomies and result in PBH. Moreover, an emergency cranioplasty could represent a safe and effective procedure in patients not responding to conservative treatment.