Coronary artery disease (CAD) has become the most common cause of mortality in the developmental countries. The association between vitamin B-6 status and inflammation is remained unclear, it might be worth to know whether vitamin B-6 is an independent or a synergic effect with inflammation in the risk of CAD. The purpose of this study was to investigate the association between plasma pyridoxal 5’-phosphate (PLP) concentration and the inflammation marker–C-reactive protein level and to estimate the relation to the risk of CAD. This study was designed as a hospital-based case-control study and performed at the Taichung Veterans General Hospital, the central part of Taiwan. Patients who were identified by cardiac catheterization as having at least 70% stenosis of one major coronary artery were assigned to the case group (n = 184). The control group (n = 516) was healthy individuals with normal blood biochemical values. All subjects’ height, weight, blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP), plasma PLP, homocysteine, high sensitivity C-reactive protein (hs-CRP), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and triglyceride were measured. Our results showed that plasma PLP concentration was negatively associated with hs-CRP level only in the control (B = -0.001, p = 0.02) but not in the CAD group. Subjects with either plasma PLP < 20 nmol/L (OR = 2.31; 95% CI: 1.21 – 4.4) or hs-CRP > 0.6 mg/dL (OR = 3.53; 95% CI: 1.62 – 7.71) significantly increased the risk of CAD. The combined presence of low PLP and higher hs-CRP level enhanced the risk of CAD and the magnitude is substantially greater (OR = 4.35; 95% CI: 1.22 – 15.48). Plasma PLP and hs-CRP is independent of each other to be associated with the increased risk of CAD, the combined presence of low PLP and high hs-CRP enhanced the risk of CAD and the magnitude is about double.