There are currently no screening methods for high grade ovarian cancer (HGOC) that guarantee effective early detection for high risk women such as germline BRCA mutation carriers. Therefore, the standard-of-care remains risk reducing salpingo-oophorectomy (RRSO) around age 40. Proximal liquid biopsy has been shown to be a promising source of biomarkers, but sensitivity has not yet qualified for clinical implementation. We report the discriminant performance of a novel proteomic classifier for detection of HGOC in high-risk population, and the safety and feasibility of simplified utero-tubal lavage (UtL) as a method for sampling proximal liquid biopsy.The training set included 93 women with high-risk for HGOC (BRCA1 and BRCA2 mutation carriers), including: 16 HGOC patients and 77 asymptomatic women, who donated UtL liquid biopsies, in 3 Israeli medical centers (Biomarkers for Early Detection of Ovarian Cancer Using Uterine Lavage (BEDOCA); ClinicalTrials.gov Identifier: NCT03150121). The proteome of the microvesicle fraction of the samples was profiled by mass spectrometry and a classifier was developed using logistic regression. An independent cohort of 104 BRCA mutation carriers was used as validation. Safety information was collected for all women who opted to UtL in a clinic setting.