Objectives: The purpose of this study was to explore the possible associations of the 5-lipoxygenase-activating protein (FLAP) poly-A genotype, plasma high-sensitivity C-reactive protein (hsCRP) and the extent score of coronary artery disease (CAD). Methods: The 17A/21A genotypes and plasma hsCRP levels were determined in 555 Chinese patients, 424 with and 131 without CAD. The luciferase reporter assay was performed to explore the functional significance of promoter poly-A polymorphism. Results: CAD patients showed significantly higher plasma hsCRP (p = 0.007) than non-CAD subjects, but no differences in the 17A allele carriers and frequency. The extent score of CAD was significantly correlated with plasma hsCRP (p = 0.03). Furthermore, the 17A allele carriers showed significantly higher hsCRP than the 21A homozygotes (p = 0.02). Multiple linear regression analysis documented an impact of the poly-A genotype on plasma hsCRP (p = 0.03). In vitro, the 17A construct was found to have greater promoter activity than the 21A construct (p = 0.02). Conclusions: The present study demonstrated a significant correlation of FLAP gene promoter 17A allele carriers with higher plasma hsCRP levels in patients with CAD. This association might be related to the increased transcriptional activity of the FLAP gene and the resulting pro-inflammatory effect on the 5-lipoxygenase pathway.