Clinical criteria/Family history-based BRCA testing misses a large proportion of BRCA carriers who can benefit from screening/prevention. We estimate the cost-effectiveness of population-based BRCA testing in general population women across different countries/health systems. A Markov model comparing the lifetime costs and effects of BRCA1/BRCA2 testing all general population women ≥30 years compared with clinical criteria/FH-based testing. Separate analyses are undertaken for the UK/USA/Netherlands (high-income countries/HIC), China/Brazil (upper–middle income countries/UMIC) and India (low–middle income countries/LMIC) using both health system/payer and societal perspectives. BRCA carriers undergo appropriate screening/prevention interventions to reduce breast cancer (BC) and ovarian cancer (OC) risk. Outcomes include OC, BC, and additional heart disease deaths and incremental cost-effectiveness ratio (ICER)/quality-adjusted life year (QALY). Probabilistic/one-way sensitivity analyses evaluate model uncertainty. For the base case, from a societal perspective, we found that population-based BRCA testing is cost-saving in HIC (UK-ICER = −5639/QALY;USA−ICER=−4018/QALY; Netherlands-ICER = −11,433/QALY),anditappearscost−effectiveinUMIC(China−ICER=18,066/QALY; Brazil-ICER = 13,579/QALY),butitisnotcost−effectiveinLMIC(India−ICER=23,031/QALY). From a payer perspective, population-based BRCA testing is highly cost-effective in HIC (UK-ICER = 21,191/QALY,USA−ICER=16,552/QALY, Netherlands-ICER = 25,215/QALY),anditiscost−effectiveinUMIC(China−ICER=23,485/QALY, Brazil−ICER = 20,995/QALY),butitisnotcost−effectiveinLMIC(India−ICER=32,217/QALY). BRCA testing costs below 172/test(ICER=19,685/QALY), which makes it cost-effective (from a societal perspective) for LMIC/India. Population-based BRCA testing can prevent an additional 2319 to 2666 BC and 327 to 449 OC cases per million women than the current clinical strategy. Findings suggest that population-based BRCA testing for countries evaluated is extremely cost-effective across HIC/UMIC health systems, is cost-saving for HIC health systems from a societal perspective, and can prevent tens of thousands more BC/OC cases
