Abstract: Objective To evaluate the impact of contrast-enhanced ultrasound （CEUS） on the diagnostic performance of ovarian-adnexal reporting and data system （O-RADS） 4-5 adnexal lesions. Methods A total of 224 patients with ovarian-adnexal lesions admitted to 10 hospitals between April 2021 and August 2023 were retrospectively enrolled. Sonographic characteristics and contrast-enhanced features were analyzed. The diagnostic performance of O-RADS, CEUS, and CEUS combined with O-RADS for O-RADS 4-5 lesions was evaluated using histopathology as the gold standard. Results A total of 232 lesions from 224 patients were included in this study, comprising 132 benign and 100 malignant lesions. O-RADS feature analysis revealed that lesion type, blood flow score, and presence of ascites were all significantly associated with malignancy in univariate analysis （all P < 0.001）. The CEUS manifestations of benign and malignant masses were distinct. The contrast-enhanced ultrasound features （enhancement morphology, time to initial enhancement, enhancement level, and washout pattern） and relative contrast parameters （arrival time,time to peak, peak intensity and area under the curve） showed statistically significant differences between the benign and malignant mass groups （all P < 0.001）. The AUC （95%CI） for differentiating benign from malignant adnexal masses in O-RADS categories 4-5 using O-RADS, CEUS, and the combination of CEUS and O-RADS was 0.716 （0.654, 0.773）, 0.793 （0.735, 0.843）, and 0.858 （0.806, 0.900）, respectively. The diagnostic accuracy of CEUS combined with O-RADS for O-RADS 4-5 lesions was significantly higher compared to either method alone （both P < 0.001）. Conclusion The combination of CEUS and O-RADS can improve diagnostic accuracy for O-RADS 4-5 lesions, providing additional valuable information to guide clinical management strategies in patients with such lesions.