Uric acid is a marker of inflammation and a risk factor for atherosclerosis that has been suggested to play a role in carotid plaque instability. Reduced atherosclerotic plaque echogenicity at ultrasound examination is associated with alarming histopathological features and inflammation. In this study, we investigated the relationship between serum uric acid (SUA) levels and echogenic patterns of plaque instability in elderly subjects with carotid atherosclerosis. Since uric acid metabolism largely depends on renal function, SUA levels were indexed for serum creatinine levels (SUA/SCr). We enrolled 108 patients aged 65 years or more (72.7 ± 5.9 years; 50 females and 58 males) who underwent carotid duplex ultrasound to evaluate plaque echogenicity by greyscale median (GSM). The regression analysis demonstrated a significant inverse association between the GSM and the SUA/SCr ratio (β: −0.567; 95% CI −0.751 to −0.384 andp< 0.0001). Stepwise multivariate regression showed that the SUA/SCr ratio explained 30.3% of GSM variability (β: −0.600; 95% CI −0.777/−0.424,p< 0.0001, and semi-partial correlation 0.303). After a mean period of 3.5 ± 0.5 years, 48 patients were reevaluated according to the same baseline study protocol. The regression analysis demonstrated a still significant inverse association between the GSM and the SUA/SCr ratio (β: −0.462; 95% CI −0.745 to −0.178 andp= 0.002). Stepwise multivariate regression showed that the SUA/SCr ratio explained 28.0% of GSM variability (coefficient −0.584, 95% CI −0.848/−0.319,p< 0.0001, and semi-partial R20.280). In conclusion, this study demonstrates that SUA levels indexed for serum creatinine are associated with the echogenic features of carotid plaque vulnerability in elderly patients with atherosclerotic disease. These data could suggest an influential role for uric acid metabolism in carotid plaque biology.