It has been postulated that large platelets may be an indicator of platelet activation, and thus be related to the extent of coronary artery disease (CAD). Platelet distribution width (PDW) directly measures the variability in platelet size. However, no data has been so far reported on this index and CAD. Thus, the aim of the current study was to investigate whether PDW is associated with the extent of CAD. We measured PDW in 1882 consecutive patients undergoing coronary angiography. Significant CAD was defined as stenosis >50% in at least one coronary vessel. We additionally measured Carotid Intima-Media Thickness (IMT) in 359 patients. Patients with higher PDW were older (p = 0.012), with higher weight (p < 0.0001) and waist (p < 0.0001), larger prevalence of diabetes (p = 0.014), dilated cardiomyopathy or valvular heart disease (p < 0.0001) and less often family history of CAD (p = 0.021), more often on statins (p = 0.005), and diuretics (p = 0.016). PDW was significantly associated with baseline glycaemia (p = 0.002) and Red Blood Cell count (p < 0.0001), but inversely related to platelet count (p < 0.0001). PDW was not associated with the prevalence of coronary artery disease (OR [95% CI] = 0.91 [0.81–1.04], p = 0.16; adjusted OR [95% CI] = 0.96 [0.82–1.12], p = 0.56). No relationship was observed between IMT and PDW as tertiles or as continuous variable (Mean IMT: r = 0.04; p = 0.46; Maximal IMT: r = 0.036, p = 0.49). This study showed that PDW is not related to the extent of CAD and carotid IMT. Thus, PDW can not be considered as a risk factor for CAD.