PURPOSE: The primary trigger for myocardial infarction and stroke is destabilization of atherosclerotic plaques. It is hypothesized that shear strain in the adventitia initiates and/or stimulates development of these plaques into rupture-prone, vulnerable plaques. Therefore, assessment of shear strain might yield a prognosis for the development of vulnerable plaques. MATERIALS AND METHODS: In simulations and phantom experiments, longitudinal shear strain was estimated using RF and envelope-based methods and compared to the applied values. Additionally, longitudinal shear strain estimates in the adventitia of six healthy volunteers were determined. RESULTS: In both experiments, the variance of the RF-based estimates was significantly smaller than that of the envelope-based estimates (Wilcoxon, p < 0.05). The periodicity of these estimates corresponded well with the cardiac cycle. The estimated values were found to be similar to previously published data. Furthermore, the signal-to-noise ratio of the shear strain estimate in the posterior wall based on RF-data was significantly higher (Wilcoxon, p 0 < 0.05) than that based on envelope-data. CONCLUSION: In conclusion, noninvasive ultrasound strain imaging using radiofrequency signals appeared to allow adequate estimation of longitudinal shear strain in the adventitial layer of the carotid artery wall.