Aim To investigate the distribution of red blood cell distribution width (RDW) and mean platelet volume (MPV) in patients with premature coronary artery disease(PCHD) and its relationship with the severity of PCHD, and to evaluate the diagnostic value of RDW and MPV for PCHD. Methods A total of 407 patients with suspected coronary artery disease(CHD) due to chest pain and male <55 years old and female <65 years old were enrolled in the study. All patients received coronary angiography (CAG), 309 cases of PCHD were confirmed and the remaining 98 cases were normal control group. The levels of RDW and MPV in the two groups and the subgroups of the PCHD were compared. The correlation between RDW and MPV and severity of coronary lesions (Gensini score) and independent risk factors for PCHD were analyzed. Results The levels of RDW and MPV in the PCHD group were significantly higher than those in the control group (P<0.05). RDW and MPV were higher in the acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP) groups than the control group (P<0.05); there was a positive correlation between RDW, MPV and Gensini scores in the PCHD group(r=0.246 and 0.199, P<0.05). Multivariate Logistic regression analysis showed that RDW and MPV were independent risk factors for PCHD(OR=3.3,5%CI:2.197~6.359, P<0.001; OR=1.3,5%CI:1.074~1.705, P=0.010). R0C curve analysis showed that the optimal cut-off value of RDW to diagnose PCHD was 12.25% with a sensitivity of 69% and specificity of 72%, and the optimal cut-off value of MPV to diagnose PCHD was 8.55 fl with a sensitivity of 91% and a specificity of 37%. Conclusions RDW and MPV are correlated to the clinical type of PCHD and the severity of PCHD. RDW and MPV are the independent risk factors for PCHD, which provides some value for the diagnosis of PCHD.