Platelets play an important role in atherothrombosis. As the most common site plaque occurs, left anterior descending artery (LAD) infarct location always associate with poor prognosis. We sought to assess whether mean platelet volume (MPV) could predict LAD infarct location and short-term clinical outcome. In this study, 190 consecutive patients with non-ST-elevation myocardial infarction (NSTEMI) were enrolled. Clinical, electrocardiography and laboratory characteristics were measured. All patients underwent coronary angiography examination and had definite culprit vessel during hospitalization. The results showed that MPV was smaller in patients with a LAD infarct location than that of left circumflex artery or right coronary artery (9.0 ± 1.5 versus 9.8 ± 1.6, p<0.001). Multivariate analysis also showed that MPV was the only independent factor to predict LAD infarct location [Odds ratio (OR)=0.65, 95% confidence interval (CI) 0.53-0.80, p<0.0001] in patients with NSTEMI. B-type natriuretic peptide and electrocardiography were unreliable predictive factors to locate culprit vessel. Receiver operating characteristic curve analysis showed MPV (area under the curve: 0.65, 95% CI 0.56-0.74, p<0.01) could reliably discriminate those patients with NSTEMI who had a major in-hospital event. Multivariate regression analyses also showed that MPV (OR=1.46, 95% CI 1.15-1.86, p<0.01) were predictors of major in-hospital events. In conclusion, MPV was the only factor independently associated with LAD infarct location in patients with non-ST-elevation myocardial infarction.