The lateral suboccipital approach for microvascular decompression (MVD) of the trigeminal nerve has become a standard-of-care over the past several decades. Syndromic cranial base settling, a rare but known cause for trigeminal neuralgia (TN), poses significant dilemmas in clinical management. In such cases, distorted anatomy may render surgery via the suboccipital approach difficult or even impossible. A 34-yr-old male with osteogenesis imperfecta and severe basilar invagination suffered from TN that was refractory to medication and stereotactic radiosurgery. MVD of the fifth nerve root was performed via a pterional trans-sylvian approach after 3-dimensional trajectory modeling suggested the feasibility of this approach. He experienced complete resolution of TN and remains free of both pain and medications after 18 mo of follow-up. This microsurgical trajectory, previously undescribed for TN, provides good visualization of the trigeminal root entry zone, thereby offering an excellent surgical option for severe TN in the setting of abnormal posterior fossa anatomy.