BACKGROUND AND IMPORTANCE: his is the first case report of clipping a cerebral aneurysm in a patient with Loeys-Dietz syndrome (LDS). LDS is a newly described autosomal dominant connective tissue disease with systemic vascular involvement. Unique to this syndrome is the development of aneurysms at a young age with the propensity of dissection or rupture at a stage that is earlier than when surgical intervention is typically indicated. We describe the nuances in intraoperative and postoperative management. CLINICAL PRESENTATION: A 31-year-old woman who recently received a diagnosis of with LDS type II presented to neurosurgical attention for management of an unruptured right ophthalmic artery aneurysm. The patient underwent a right pterional craniotomy for clipping of the aneurysm, with lumbar drain placement before the procedure. Papaverine had to be used several times to counteract vasospasm of the vessels during arachnoid dissection. Because of vascular reactivity, temporary clipping was not used, and the aneurysm was clipped successfully. CONCLUSION: LDS is a newly described disorder that warrants awareness in the neurosurgical community because of its association with intracerebral aneurysms as well as craniosynostosis (19%), scoliosis (20%), cervical spine instability (7%), hydrocephalus, and Arnold-Chiari malformation. When clipping aneurysms in these patients, the surgeon should be aware of the potential for severe vascular reactivity during dissection and avoid temporary clipping when possible. Avoidance of lumbar drainage intraoperatively reduces the risk of intracranial hypotension after removal.