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Staged subpectoral expander-implant breast reconstruction is widely performed. Disruption of the pectoralis major origin and the frequent occurrence of animation deformity and functional discomfort associated with subpectoral reconstruction remain ongoing concerns. Prepectoral single-stage direct-to-implant reconstruction resolves many of these issues. In this study, the authors explored the rationale for prepectoral single-stage implant-based breast reconstruction with anterior AlloDerm coverage as an alternative to the staged approach.Seventy-three breasts in 50 patients were reconstructed using a single-stage direct-to-implant prepectoral approach with total anterior AlloDerm coverage during a 24-month period. The decision to proceed with single-stage reconstruction was predicated upon the adequacy of mastectomy skin flap blood flow based on indocyanine green fluorescence perfusion assessment. The patients were followed up for a maximum of 32 months.Ninety-seven percent of patients achieved complete healing within 8 weeks. There were 2 implant losses (2.7%) due to infection. Major seroma rate requiring repeated aspiration and drain insertion was 1.2%. There were no full-thickness skin losses. Capsular contracture was 0% in nonradiated patients. There were no cases of animation deformity. The authors were unable to establish significant correlation between complications and any of the usually stated risk factors, such as smoking, obesity, and large mastectomy weights, presumably due to the rigorous application of intraoperative skin perfusion assessment.Single-stage direct-to-implant reconstruction using a prepectoral approach appears to be a safe and effective means of breast reconstruction in many patients, assuming adequate skin perfusion is present.