Introduction. Microvascular tissue serves as the foundation for tissue granulation and remodeling during the wound healing process. Optimal repair of microvascular structure and function is essential for future healing capacity and to minimize tissue breakdown in a newly epithelialized wound. Objective. This case series of 3 patients with nonhealing diabetic foot ulcers (DFUs) refractory to standard wound care demonstrates the ability of processed microvascular tissue (PMVT) to enable wound closure, increase local perfusion and vascular maturity, and improve overall tissue quality. Materials and Methods. Three patients with nonhealing DFUs ranging from 1.1 cm2 to 11.2 cm2 recalcitrant to standard of care were treated weekly with topical PMVT and standard of care. Wound closure was measured weekly using infrared imaging. Fluorescence microangiography was used to perform dynamic quantification of wound microcirculation and assess the perfusion quality. Ingress rates were measured at 5 defined rectangular regions of interest of the wound to evaluate inflammation and microvascular integrity. Results. All 3 nonhealing DFUs treated with weekly topical PMVT healed within 12 weeks (average, 6.3 ± 5.5 weeks). Assessment of healed wounds at the time of closure indicated PMVT treatment significantly improved perfusion within the newly healed wounded area and throughout the immediate surrounding tissues. No wound recurrence or tissue deterioration has been observed in more than 9 months of follow-up. Conclusions. In this series of patients, the PMVT graft demonstrated improved wound closure, increased local perfusion and vascular maturity, and improved tissue quality. This graft is a promising advanced tissue therapy for nonhealing DFUs and other complex wounds. It is now the subject of a randomized controlled trial.