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Summary: Adequate tissue perfusion is essential to minimize postoperative complications following microsurgery. Intraoperative knowledge of tissue perfusion could aid surgical decision-making and result in reduced complications. Laser speckle imaging is a new, noninvasive technique for mapping tissue perfusion. This article discusses the feasibility of using laser speckle imaging during free flap breast reconstruction and its potential to identify areas of inadequate perfusion, thus reducing surgical complications. Adult patients scheduled to undergo free flap breast reconstruction were recruited into the study. Laser speckle images were obtained from the abdominal and breast areas at different stages intraoperatively. Zonal perfusion was compared with the Holm classification and clinical observations. Twenty patients scheduled to undergo free flap breast reconstruction were recruited (23 reconstructed breasts) (mean age, 50 years; range, 32 to 68 years). Flap zonal perfusion was 238 (187 to 313), 222 (120 to 265), 206 (120 to 265), and 125 (102 to 220) perfusion units for zones I, II, III, and IV, respectively (analysis of variance, p < 0.0001). Zonal area with perfusion below an arbitrary perfusion threshold were 20 (0.3 to 75), 41 (3 to 99), 49 (9 to 97), and 99 (25 to 100) percent, respectively (analysis of variance, p < 0.0001). One example is presented to illustrate potential intraoperative uses for laser speckle imaging. This study shows that laser speckle imaging is a feasible, noninvasive technique for intraoperative mapping of tissue perfusion during free flap breast reconstruction. Zonal tissue perfusion was reduced across the Holm classification. Observations indicated the potential for laser speckle imaging to provide additional information to augment surgical decision-making by detection of inadequate tissue perfusion. This highlights the opportunity for surgeons to consider additional aids for intraoperative tissue perfusion assessment to help reduce perfusion-related complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.