Background/Objectives: Pyoderma gangrenosum (PG) is a rapidly progressive, ulcerating condition that can cause large, painful lesions when uncontrolled. There is currently no standard of care treatment for severe PG ulcers refractory to systemic treatment. The present study aims to characterize the outcomes of placental allografts in treating severe PG lesions. Methods: A single institution retrospective chart review was conducted at the University of South Florida affiliated sites examining PG patients that received placental allograft treatment. Results: The review returned five patients with clinically diagnosed or biopsy-proven PG treated with placental allograft. In all five patients, application of placental allograft resulted in varying degrees of short-term (<1 month) improvement. Near-complete resolution was observed in one patient. Out of the 20 total allografts placed between the 5 patients, only one had an adverse event of infection within one week of placement. Grafts were otherwise very well tolerated by all patients. Conclusions: Placental allografts show promising adjunctive therapeutic potential for severe PG lesions with preliminary findings showing good viability and safety profiles. Future prospective controlled studies should be performed to further examine the viability of this adjunctive treatment in this disease.