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SPY Elite imaging uses an injectable fluorescing agent to intraoperatively assess the perfusion and viability of tissue, including skin flaps, during postmastectomy reconstruction for breast cancer patients. In this study, the authors sought to compare the surgeon’s assessment of flap viability with that of SPY imaging perfusion, analyzing the clinical outcomes postoperatively.In this study, the intraoperative difference between the plastic surgeon’s assessment of skin viability and the SPY imaging assessment was analyzed by the skin flap area preserved in patients undergoing skin-sparing mastectomy. After the mastectomy, the operating surgeon marked the area of the skin flap to excise; then, the SPY imaging was performed and photographs and videos of the perfusion were collected. The skin flap was resected before implant or tissue expander placement according to the plastic surgeon’s assessment. The patients were routinely followed up in the clinic postoperatively.A total of 55 breasts were analyzed. The surface area of diminished perfusion was significantly greater in the SPY imaging compared with the surgeon’s assessment.In this study, intraoperative indocyanine green angiography was found to be conservative in its estimation of viability and, if followed, would result in a more aggressive resection than the area deemed viable by the operating surgeon. Based on the results, intraoperative indocyanine green angiography should be used in settings where perfusion is clinically assessed as marginal. It likely does not play a useful role in lower risk cases where the operating surgeon identifies no areas of concern.Diagnostic, IV.