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Prosthetic breast reconstruction is most commonly performed using the two-stage (expander-implant) technique. However, with the advent of skin-sparing mastectomy and the use of acellular dermal matrices, one-stage prosthetic reconstruction has become more feasible. Prior studies have suggested that one-stage reconstruction has economic advantages relative to two-stage reconstruction despite a higher revision rate. This is the first cost-utility analysis to compare the cost and quality of life of both procedures to guide patient care.A comprehensive literature review was conducted using the MEDLINE, EMBASE, and Cochrane databases to include studies directly comparing matched patient cohorts undergoing single-stage or staged prosthetic reconstruction. Six studies were selected examining 791 direct-to-implant reconstructions and 1142 expander-implant reconstructions. Costs were derived adopting both patient and third-party payer perspectives. Utilities were derived by surveying an expert panel. Probabilities of clinically relevant complications were combined with cost and utility estimates to fit into a decision tree analysis.The overall complication rate was 35 percent for single-stage reconstruction and 34 percent for expander-implant reconstruction. The authors’ baseline analysis using Medicare reimbursement revealed a cost decrease of $525.25 and a clinical benefit of 0.89 quality-adjusted life-year when performing single-stage reconstructions, yielding a negative incremental cost-utility ratio. When using national billing, the incremental cost-utility further decreased, indicating that direct-to-implant breast reconstruction was the dominant strategy. Sensitivity analysis confirmed the robustness of the authors’ conclusions.Direct-to-implant breast reconstruction is the dominant strategy when used appropriately. Surgeons are encouraged to consider single-stage reconstruction when feasible in properly selected patients.