Background: In reconstructive surgery, adequate perfusion of flaps is essential for successful outcomes. Assessing normal flap perfusion and differentiating it from problematic perfusion is important and time-consuming. Laser speckle contrast imaging (LSCI), an optical technique for quantitative microcirculation assessment, can be used to non-invasively monitor flap perfusion. We designed a wireless handheld LSCI device and investigated its clinical feasibility in Deep Inferior Epigastric Perforator (DIEP) flap reconstruction surgery. Methods: In a case series study with 15 patients and 20 DIEP flaps, perfusion was measured perioperatively across the 4 Hartrampf zones at 4 specific time points and on the first post-operative day. Results: In unilateral reconstructions, the perfusion in dissected flaps showed a perfusion gradient across the zones, with the highest perfusion in zone I and lowest perfusion in zone IV. The decrease in perfusion between unilateral flap elevation and temporary occlusion measurements was detected in unilateral flaps, but not in bilateral flaps. The device could detect flap failure in 2 cases by measuring anomalous perfusion values. Conclusions: The results indicate that our device is potentially valuable for flap monitoring. It detected differences in perfusion throughout the flap zones, a decrease in perfusion when clamping the pedicle and anomalous perfusion in flaps that failed. Motion artefact correction is needed to measure reliably during motion caused by patient breathing, pulse and operator motion. Further studies are needed to determine whether the wireless perfusion imager enables the early detection of complications, which could aid in prevention or prompt reintervention to salvage a flap.