The complement system consists of a family of proteins that play a critical role in the innate immune system. Complement activation has been implicated in many chronic inflammatory diseases, including atherosclerosis. However, a number of experimental studies have highlighted a beneficial role of component C1q in early atherosclerosis and in diabetes mellitus (DM). Despite these data, there have been no studies that have specifically examined the utility of plasma complement C1q as a clinical biomarker in patients with known or suspected coronary artery disease. In this study, baseline plasma complement C1q levels were measured in 159 men with DM who were referred for coronary angiography and who were followed up prospectively for the development of all-cause mortality for 10 years. After adjustment for baseline clinical, angiographic, and laboratory parameters, reduced plasma complement C1q levels were an independent predictor of all-cause mortality at 10 years (hazard ratio 0.66, 95% confidence interval 0.52 to 0.84, p = 0.0006). In additional multivariate models that adjusted for a variety of biomarkers with established prognostic efficacy, complement C1q remained an independent predictor of all-cause mortality at 10 years. In conclusion, reduced levels of complement C1q are associated with an increased risk of all-cause mortality at 10 years in patients with DM referred for coronary angiography. Furthermore, this association is independent of a variety of clinical, angiographic, laboratory variables, including biomarkers with established prognostic efficacy in the prediction of adverse cardiovascular outcomes.