Neovascularization of a carotid atherosclerotic plaque (AP) is associated with an increased risk of stroke. Contrast-enhanced ultrasonography (CEUS) is a widely used method for imaging intraplaque neovascularization in vivo. Unfortunately, there are no standardized guidelines for CEUS interpretation. The aim of this study was to identify the most reliable method for CEUS-based assessment of AP neovascularization. Seventy-eight AP were removed during carotid endarterectomy in 73 patients, of whom 5 had AP on both sides, and examined morphologically. All patients underwent preoperative duplex scanning and CEUS; Sonovue was used as a contrast agent. AP neovascularization was assessed on a 4-grade visual scale and with 3 different quantitative methods using QLAB software. On the visual scale (method 1), poorly (37%) and moderately (51%) vascularized plaques were the most common. Quantitative analysis (data were presented as Ме (Q1; Q3)) revealed that the number of blood vessels per 1 cm2 of the plaque (method 2) was 16 (10; 26), the ratio of the total vessel area to the plaque area (method 3) was 6% (3; 9), and AP ROI (method 4) was 2.6 dB (1.8; 4.1). Significant correlations were demonstrated between the results produced by method 2 and method 3 (р < 0.0001), method 3 and method 2 (р = 0.0006), and between pathomorphological findings and the results produced by methods 1–3, especially method 2 (р < 0.004). AP ROI brightness did not correlate with other results. The presence of hyperechoic components (calcifications) in AP dramatically reduced the reliability of US-based intraplaque neovascularization assessment. The most accurate CEUS-based quantitative method for assessing intraplaque neovascularization is estimation of blood vessel number per 1 cm² of the plaque.