Background The Ovarian-Adnexal Reporting and Data System (O-RADS) US risk stratification and management system (O-RADS US) was designed to improve risk assessment and management of ovarian and adnexal lesions. Validation studies including both surgical and nonsurgical treatment as the reference standard remain lacking. Purpose To externally validate O-RADS US in women who underwent either surgical or nonsurgical treatment and to determine if incorporating acoustic shadowing as a benign finding improves diagnostic performance. Materials and Methods This retrospective study included consecutive women who underwent pelvic US between August 2015 and April 2017 at a tertiary referral oncology center. Two independent readers blinded to clinical and histologic outcome assigned an O-RADS risk category and an International Ovarian Tumor Analysis (IOTA) Assessment of Different NEoplasias in the adneXa (ADNEX) model risk of malignancy score to assessable lesions. Reference standards were surgical histopathology or 2-year imaging follow-up. Receiver operating characteristic (ROC) curve analysis was used to evaluate performance of the O-RADS US, ADNEX, and modified O-RADS models incorporating acoustic shadowing. Results In total, 227 women (mean age, 52 years ± 16 [SD]) with 262 ovarian or adnexal lesions were evaluated. Of these lesions, 187 (71%) were benign and 75 (29%) were malignant. The proportion of malignancy was 0% (0 of 100) for O-RADS 2, 3% (one of 32) for O-RADS 3, 35% (22 of 63) for O-RADS 4, and 78% (52 of 67) for O-RADS 5. The area under the ROC curve (AUC) for O-RADS and ADNEX was 0.91 (95% CI: 0.88, 0.94) and 0.95 (95% CI: 0.92, 0.97; P = .01), respectively. The addition of acoustic shadowing as a benign finding improved O-RADS AUC to 0.94 (95% CI: 0.91, 0.96; P = .01). Use of O-RADS 4 as a threshold yielded a sensitivity of 99% (74 of 75; 95% CI: 96, 100) and a specificity of 70% (131 of 187; 95% CI: 64, 77). Conclusion In a tertiary referral oncology center, the Ovarian-Adnexal Reporting and Data System US risk stratification and management system enabled accurate distinction of benign from malignant ovarian and adnexal lesions. Adding acoustic shadowing as a benign finding improved its diagnostic performance. © RSNA, 2022 See also the editorial by Levine in this issue.