Purpose: Women who inherit a BRCA1 or BRCA2 pathogenic variant are at high risk of developing breast and ovarian cancer. Evidence for the effectiveness and cost-effectiveness of long-term management in clinical practice is lacking. The purpose of this study was to evaluate the real-world cost-effectiveness of BRCA carrier management within a structured clinical program. Methods: Lifetime health outcomes and costs of clinical management for female unaffected BRCA carriers aged 20 were measured using a microsimulation model. For the intervention, women could attend a high-risk clinic, undergo risk-reducing surgery, and receive annual breast screening. Input data for the model was from a clinical database of 983 BRCA carriers. The comparator was no risk management. Outcomes were discounted at 5%. Results: The incremental cost-effectiveness ratio for the program was $32,359 to $48,263 per quality-adjusted life-year (QALY). Limiting uptake of risk-reducing salpingo-oophorectomy to <50% of carriers decreased cost-effectiveness by $7000–8000 per QALY. Achieving perfect adherence to guidelines was less cost-effective for BRCA2 due to increased risk-reducing mastectomy costs with smaller incremental health benefit. Conclusion: Long-term management of BRCA carriers within a structured clinical program is cost-effective. Suboptimal adherence to risk management guidelines can substantially affect outcomes and is an important consideration for future studies.