Prospective evaluation of apolipoprotein E (APOE) genotypes in 106 consecutive patients with stenosis of the cervical spinal canal. To determine the association between cervical spondylotic myelopathy (CSM) in patients with chronic spinal cord compression and the APOE genotype. The APOE allele epsilon 4 is a risk factor for the occurrence, progression, and poor outcome in several neurologic diseases. Information of the association between APOE genotype and CSM in the literature are lacking so far. One hundred six consecutive patients with chronic cervical spinal cord compression due to stenosis of the spinal canal were evaluated prospectively. APOE genotypes were determined by polymerase chain reaction followed by restriction enzyme digestion and sodiumdodecylsulfate poyacrylamide gel electrophoresis (SDS PAGE) of digested fragments. Clinical and radiologic variables evaluated were age, occurrence of CSM, duration of symptoms, number of affected segments, and diameter of spinal canal of most affected segment. Univariate association between variables was tested. A backward stepwise method was used to construct multivariate logistic regression models in relation to the occurrence of CSM as dependent variable. The following distribution of APOE genotypes was found: epsilon 2 epsilon 2 3 patients (2.8%), epsilon 2 epsilon 3 9 patients (8.5%), epsilon 2 epsilon 4 1 patient (0.9), epsilon 3 epsilon 3 67 patients (63.2%), epsilon 3 epsilon 4 24 patients (22.6%), epsilon 4 epsilon 4 2 patients (1.9%). Univariate analysis showed that patients with chronic spinal cord compression and homo- or heterozygous allele epsilon 4 are more likely to develop CSM than patients without allele epsilon 4 (65.0% vs. 35.0%, P < 0008; OR 3.5; 95% CI 1.3-9.8). This effect remained significant in a binary logistic regression model adjusted to other known risk factors for CSM. Inclusion of the variable homo- or heterozygous epsilon 4 allele led to an increased goodness of fit of the model compared with the model without epsilon 4. CONCLUSION.: This study supports the hypothesis that the APOE epsilon 4 allele increases the risk of CSM in patients with chronic cervical spinal cord compression; however, a larger prospective population-based study is needed to answer this question definitively.