Open replacement of multifocal aortic aneurysms is an operative and clinical challenge. Thoughtful consideration of both surgical technique and timing is important to reduce risk of major cardiovascular and neurologic complications. We discuss the management of a 34-year-old male with suspected connective tissue disease admitted with multifocal, giant aneurysms of his right subclavian artery, ascending and aortic arch, descending and abdominal aorta, and right iliac artery. A complex, open three-stage repair was undertaken. Genetic testing revealed a missense MYH11 mutation. We describe our approach and patient outcome.