The objective of this study was to investigate the effects of low serum bilirubin levels on the risk for future coronary artery disease (CAD) in a prospective cohort. CAD events were examined according to baseline serum bilirubin levels in a prospective large-scale, community-based Korean cohort in 2 subsequent prospective biennial surveys. A total of 8,593 subjects were included, 0.9% of whom reported newly developed CAD events during the 4 years of follow-up. Cox regression analyses showed that the lowest serum total bilirubin level category (bilirubin ≤0.32 mg/dl) was an independent risk factor for future CAD events (adjusted hazard ratio [HR] 1.890, 95% confidence interval [CI] 1.088 to 3.284; p = 0.024). Subjects with metabolic syndrome had a higher risk for future CAD events than those without metabolic syndrome (HR 3.366, 95% CI 2.079 to 5.448, p <0.001). Low bilirubin levels increased the CAD risk in subjects with metabolic syndrome further (HR 2.016, 95% CI 1.069 to 3.800; p = 0.030), with these subjects showing a >6 times higher risk for CAD than subjects with bilirubin levels >0.32 mg/dl and no metabolic syndrome (HR 6.228, 95% CI 3.118 to 12.437; p <0.001). In conclusion, the addition of low serum bilirubin levels to the traditional risk factors for CAD, such as metabolic syndrome, may yield an improvement of risk prediction.