Numerous techniques are used for septal perforation repair, yet success rates remain variable. Few studies have evaluated the effectiveness of interposition grafts of polydioxanone plates combined with a temporoparietal fascia graft for septal perforation repair. To investigate and describe the use of interposition grafts of polydioxanone plates combined with a temporoparietal fascia graft for septal perforation repair and the expansion of this technique to patients with more challenging comorbidities, including granulomatosis with polyangiitis. A retrospective medical record review was performed of patients who underwent septal perforation repair using interposition grafts of polydioxanone plates combined with a temporoparietal fascia graft from January 1, 2015, to July 1, 2018, at Vanderbilt University Medical Center and from January 1, 2017, to July 1, 2018, at the University of Iowa. All patients underwent septal perforation repair with interposition grafts of polydioxanone plates and a temporoparietal fascia graft. Assessing closure of septal perforation was the primary outcome. Secondary outcomes were resolution of presenting symptoms of septal perforation, area of perforation, length of postoperative stent and silastic sheeting placement, postoperative complications and resolution, and duration of follow-up. Preoperative and postoperative Nasal Obstruction Symptom Evaluation (NOSE) scores were assessed. A total of 17 patients (12 women and 5 men; mean [SD] age, 45 [15] years) were included. The causes of perforations were iatrogenic (9 [53%]), rheumatologic (2 [12%]), and unknown or idiopathic (6 [35%]). Patients most commonly presented with nasal crusting (12 [71%]), whistling (9 [53%]), nasal obstruction (9 [53%]), and epistaxis (5 [29%]). Mean (SD) perforation size was 0.99 (1.04) cm2. Mean (SD) postoperative follow-up was 6.1 (4.1) months. A total of 15 patients (88%) had complete resolution of presenting symptoms at last follow-up. All perforations were closed with overlying mucosa at the most recent follow-up examination. Nine of 17 patients completed both preoperative and postoperative NOSE. There was a significant difference between the mean (SD) preoperative and postoperative NOSE scores (62.78 [27.74] vs 17.78 [15.83]; P = .004). Repair of symptomatic nasal septal perforations using a temporoparietal fascia graft combined with a polydioxanone plate was associated with positive outcomes. Repair of septal perforations caused by rheumatologic disease, including granulomatosis with polyangiitis, can be considered for repair using this technique. Resolution of symptoms appeared to be clinically more meaningful in evaluation of septal perforation repair than rate of perforation closure, and the NOSE scale has the potential to serve as an objective corroboration to patient-reported postoperative outcomes. 4.