OBJECTIVES: To examine whether the decrease in IMT progression rate in the carotid bulb induced by metoprolol CR/XL treatment (25mg once daily) observed in the β-blocker Cholesterol-lowering Asymptomatic Plaque Study (BCAPS) was accompanied by an effect on carotid plaque echogenicity. METHODS: Gray scale median (GSM) in carotid plaques, used as a score of echogenicity, was measured at baseline and after 36 months in those 341 subjects (aged 49-69 years) with an asymptomatic moderate- to large-sized carotid plaque present at baseline and at follow-up. Participants were in a factorial design assigned to treatment with metoprolol CR/XL (25mg once daily), fluvastatin (40mg once daily) or corresponding placebo. RESULTS: After 36 months plaques were more echogenic in participants treated compared to those not treated with metoprolol CR/XL (57.3±16.8 versus 51.8±20.0, p=0.006). GSM had increased more from baseline in the metoprolol CR/XL treated subjects (25±15 versus 18±20, p<0.001), and plaques that had become more echolucent were less frequent in the metoprolol CR/XL treated subjects (3.6% versus 17.0%, p<0.001). CONCLUSIONS: Long-term treatment with low dose metoprolol CR/XL in clinically healthy subjects with moderate-sized carotid plaques was associated with increase in plaque echogenicity, suggesting a potential beneficial effect of the β-blocker treatment on plaque stability.