We report an unanticipated medication effect resulting in near-complete wound healing in a patient after beginning tadalafil therapy of 20 mg thrice daily. This patient was treated for 50 years with state-of-the art acute and then chronic wound interventions after a traumatic farm machinery accident which resulted in a devascularised foot wound. This infection was both life- and limb-threatening. The patient had undergone multiple vascular and plastic surgeries and antimicrobial therapies in addition to hospitalisations for sepsis. Limb amputation was being considered, when his urologist placed him on daily phosphodiesterase-5 inhibitor therapy, prior to unrelated urologic surgery. Remarkably, his foot wound underwent near-complete resolution and has been stable for 2 years.