Background: Despite the presence of only a few established risk factors, some patients will experience atherosclerotic events. Therefore, methods for improved risk stratification for atherosclerotic events are wanted. We aimed to detect changes in carotid artery atherosclerotic plaque volume and echogenicity over time in patients with an acute thromboembolic event and in patients with chronic atherosclerotic disease, both treated with statin, using a novel 3D ultrasound system. Methods: We included two cohorts of patients; 70 patients, naïve to statin treatment, admitted with acute, first-time myocardial infarction (aMI), and 69 patients who had been on statin treatment for a minimum of 6 months with chronic peripheral arterial disease (cPAD). 3D ultrasound examination was performed at baseline and after 3 and 12 months. Plaque volume was quantified in 3D ultrasound plaque acquisitions, and echogenicity was assessed using grayscale median (GSM) and normalized with adventitia as reference. Results: The aMI group had darker plaques than the cPAD group at baseline (mean GSM: 60.98, standard deviation (SD): 24.09 vs. 71.75, SD: 21.55; P = 0.006), 3 months (63.64, SD: 20.47 vs. 73.44, SD: 20.46; P = 0.006) and at 12 months follow-up (59.25, SD: 18.07 vs. 71.02, SD: 22.31; P = 0.004). The differences were not significant after adjusting for traditional risk factors. Dividing both groups by the median GSM, the darkest half of the aMI group's had an increase in GSM mainly within the first 3 months (10.49, CI 95%: 2.45 to 18.53; P = 0.012) and hereafter remained unchanged at 12 months follow-up (−0.53, CI 95%: −7.28 to 6.22, P = 0.875). In the darkest cPAD group GSM also increased within 3 months (8.14, CI 95%: 1.85–14.32, P = 0.012) and hereafter stabilized till 12 months (−2.54, CI 95%: −9.62 to 4.53, P = 0.475). Plaque volume did not change in the aMI group from baseline (median: 55.41 mm³, interquartile range (IQR): 24.24–84.31) to 12 months (58.67 mm³, IQR: 31.81–93.51) (P = 0.220) whereas there was a small decrease in the cPAD group from baseline (71.63 mm³, IQR: 40.12–135.61) to 12 months (67.73 mm³, IQR: 31.00–122.38) (P = 0.026). Conclusions: Echolucent carotid plaque, assessed with the novel 3D matrix ultrasound system, had increasing GSM within 3 months period, indicating stabilization of the more vulnerable plaques in aMI and cPAD patients. Plaque volume decreased over 12 months follow-up in a long-term statin-treated patient with cPAD, but not during the first 12 months statin therapy in patients with aMI.