Background: Data concerning the relationship between cardiovascular risk factors, plasmatic markers, carotid disease and extent of coronary lesions are lacking. Objectives: To evaluate the role of cardiovascular risk factors, plasmatic levels of high sensitivity C-reactive protein (hs-CRP), fibrinogen, lipoprotein(a), and carotid plaque extension in predicting the severity of coronary artery disease (CAD). Methods: We analyzed 574 subjects undergoing first coronary angiography. For angiographic analysis, we used the Syntax Score and we defined the prognostic localization of CAD as a critical stenosis of the left main and/or proximal segment of left anterior descending artery. Levels of hs-CRP > 3 mg/L, lipoprotein(a) plasma levels > 30 mg/dL and plasma fibrinogen > 300 mg/dL were considered critical. Significant carotid disease (SCD) was defined by the presence of lesions producing a 50% diameter stenosis with a peak systolic velocity > 125 cm/s. A mean carotid intima media thickness (IMT) > 0.9 mm was considered abnormal. Results: In the adjusted analysis the presence of SCD was found to be an independent predictor of high Syntax Score (p < 0.001), while high fibrinogen levels were independently associated with the presence of CAD in prognostic localization (p = 0.04). In the sub-group of patients without SCD, IMT > 0.9 mm was found to be an independent predictor of the presence of CAD (p < 0.001). Conclusions: SCD strongly predicts high Syntax Score, while IMT shows excellent positive predictive value for the presence of CAD. In addition, high plasma fibrinogen levels are associated with coronary stenoses in prognostic localization. © 2017 Elsevier B.V.