Twenty-seven cases of craniovertebral junction compression treated with transoral surgery were reviewed to assess the influences of pathological processes and surgical interventions on spinal stability. All patients presented with signs and symptoms of spinal-cord or brain-stem dysfunction. Pathology included rheumatoid arthritis in 11 patients, congenital osseous malformations in 11, spinal fractures in two, plasmacytoma in one, osteomyelitis in one, and a gunshot injury in one. Instability was defined as clear radiographic evidence of mobile subluxation in conjunction with clinical assessment. Of 19 patients (70%) requiring internal fixation, nine underwent upper cervical fusion and 10 had occipitocervical fusion. When instability occurred, all subluxations were at the C1-2 level. There were no occipito-atlantal subluxations. Eight patients (30%) had preoperative instability of the craniovertebral junction due solely to their pathology, 11 patients (40%) suffered instability after transoral surgery, and eight (30%) were without clinical or radiographic evidence of instability (mean follow-up period 14 months). Craniovertebral junction instability predominated among patients with rheumatoid arthritis: 91% required fusion and 45% presented with pre-existing instability. Among individuals with congenital osseous malformations, 45% required fusion and only one patient (9%) had pre-existing instability. Patients who required subsequent posterior decompression of a Chiari malformation were at risk for developing instability; three of four became unstable after posterior decompression. Transoral resection of the dens, the anterior arch of C-1, and the lower clivus does not fully destabilize the spine; however, this operation may potentiate incipient pathological instability. The primary determinants of instability are the extent of pathological bone destruction, ligamentous weakening, and operative bone removal. Long-term follow-up monitoring is needed after transoral surgery to detect cases of late instability.