Study design: Prospective mortality study. Objective: To assess the relationship between comorbid medical conditions and other healthrelated factors to mortality in chronic spinal cord injury (SCI). Setting: Boston, MA, USA. Methods: Between 1994 and 2000, 361 males X1 year after injury completed a respiratory health questionnaire and underwent pulmonary function testing. Cause-specific mortality was assessed over a median of 55.6 months (range 0.33-74.4 months) through 12/31/2000 using the National Death Index. Results: At entry, mean (7SD) age was 50.6715.0 years (range 23-87) and years since injury was 17.5712.8 years (range 1.0-56.5). Mortality was elevated (observed/expected deaths ¼ 37/ 25.1; SMR ¼ 1.47; 95% CI ¼ 1.04-2.03) compared to US rates. Risk factors for death were diabetes (RR ¼ 2.62; 95% CI ¼ 1.19-5.77), heart disease (RR ¼ 3.66; 95% CI ¼ 1.77-7.78), reduced pulmonary function, and smoking. The most common underlying and contributing causes of death were diseases of the circulatory system (ICD-9 390-459) in 40%, and of the respiratory system in 24% (ICD-9 460-519). Conclusions: These results suggest that much of the excess mortality in chronic SCI is related to potentially treatable factors. Recognition and treatment of cardiovascular disease, diabetes, and lung disease, together with smoking cessation may substantially reduce mortality in chronic SCI.Spinal Cord (2005) 43, 408-416.