OBJECTIVE Metastatic epidural spinal cord compression (MESCC) is a relatively common and debilitating complication of metastatic disease that often results in neurological deficits. Pathological fractures of the vertebral body in patients with MESCC are not uncommon. The goals of this study were to evaluate the effects of compression fractures on long-term neurological function, as well as understand the factors that predict the development of pathological fractures for patients with MESCC. METHODS One hundred sixty-two patients undergoing decompressive surgery for MESCC at an academic tertiary care institution from 1995 to 2007 were retrospectively reviewed. Multivariate proportional hazards regression analysis was used to assess the effects of pathological vertebral body fractures on ambulatory outcome, whereas multivariate logistical regression analysis was used to identify factors associated with preoperative compression fractures. RESULTS Sixty and 102 patients presented with and without pathological vertebral body fractures, respectively, and MESCC. Patients were followed for a mean of 9.7 +/- 2.6 months. The presence of preoperative compression fractures was independently associated with decreased postoperative ambulatory status (odds ratio, 2.106; 95% confidence interval, 1.123-4.355; P = 0.03). This was independent of age, preoperative ambulatory status, preoperative motor deficit, duration of preoperative symptoms, immediate postoperative motor deficit, and lytic tumor appearance. The factors strongly associated with preoperative compression fractures in this study include lack of sensory deficits (P = 0.01), primary breast cancer (P = 0.008), anterior spine metastases (P = 0.005), thoracic spine involvement (P = 0.01), preoperative chemotherapy (P = 0.03), and, possibly, preoperative radiation therapy (P = 0.16). CONCLUSIONS The findings of this study may provide insight into risk stratifying as well as guiding surgical management for patients with MESCC.