Background Onyx liquid embolic system has been used in the treatment of intracranial aneurysm and arteriovenous malformation since 1999. Recently, Onyx HD-500 has been especially advocated for the treatment of large and giant intracranial aneurysms. Methods Two cases of cranial nerve palsy following embolization of unruptured symptomatic giant cavernous internal carotid artery aneurysms are presented. The first patient had a right 2.0cm x 1.5cm cavernous aneurysm, and the second a 2.7cm x 1.8cm left cavernous aneurysm. Both patients developed persistent diplopia after embolization with Onyx HD-500. Results Ophthalmological evaluation revealed that both patients had abductor nerve palsy on the same side as the aneurysm; in addition the second patient also had ipsilateral occulomotor nerve palsy. Conclusion Embolization of giant cavernous aneurysm with Onyx HD-500 can result in worsening or development of new cranial nerve palsies; possibly from mass effect resulting from edema and thrombosis of the aneurysm in the cavernous sinus.