Abstract In order to easily identify high-risk population of breast cancer and to determine the optimal screening modality among Chinese high-risk women, a total of 33234 asymptomatic Chinese women aged 45-65 years underwent breast ultrasound (BUS) and mammography (MAM) screening concurrently. Physicians performed these screening modalities separately and blindly. The number of risk factors of breast cancer, rather than complex risk prediction models, was used to identify potential high-risk women. Initially, a total of 13 factors (age at menarche, menopausal status, age at menopause, number of live birth, age at first pregnancy, breast feeding, duration of breast feeding, abortion, oral contraceptive, hormone replacement therapy, obesity, history of benign breast disease, and family history of breast cancer) were selected. After excluding correlated factors, factors with risk frequency ≥ 20% and factors with missing values ≥ 5%, 6 factors (age at menarche, age at menopause, age at first pregnancy, oral contraceptive, obesity, family history of breast cancer) were selected as risk-evaluating factors. High-risk women was defined as those with ≥ 1 of the abovementioned 6 factors. According to this strategy, the detection rate among high-risk women (4.34/1000) was significantly higher than their counterpart (2.23/1000, p=0.001), and the percent of high-risk women accounted for 34.9% of the whole population. . Among high-risk women, the cancer detection rate on MAM (3.2/1000) was non-significantly different from that on BUS (3.1/1000; p=0.663). Comparisons on screening accuracy showed no significant difference on sensitivities (73.9% vs. 68.8%, p=0.663), positive prediction values (14.1% vs. 18.5%, p=0.221), and negative prediction values (99.9% vs. 99.9%, p=0.574) between MAM and BUS, but significant higher specificity for BUS (98.6%) than MAM (98.0%, p=0.001). Comparisons on cancer characteristics showed no significant difference on breast carcinoma in situ (22.6% vs. 17.2%, p=0.605), lymph-node involvement (24.1% vs. 20.0%, p=0.715), and tumor size ≥ 2 cm (25.0% vs. 35.5%, p=0.350) between MAM-detected cancers and BUS-detected cancers. Subgroup analyses stratified by breast densities (four groups: 0~ <25, 25 ~ 50, 51 ~ 75, >75%) or age at enrolment (four groups: ≤49, 50-54, 55-59, ≥60 years) also showed no significant difference on sensitivities between MAM and BUS across subgroups. In conclusion, high-risk screening strategy based on the number of exposure to risk factors is an easy-to-use method to identify potential high-risk women of breast cancer, and the performance of BUS is very similar to that of MAM among high-risk women. Citation Format: Yubei Huang, Fengju Song, Kexin Chen. Screening performance of ultrasonography and mammography among Chinese women at high-risk of developing breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5295. doi:10.1158/1538-7445.AM2017-5295