Background The surgical outcomes following tympanic membrane (TM) repair are affected by many factors. Objectives To evaluate the efficacy of endoscopic porcine small intestine submucosa graft (PSISG) myringoplasty by comparing with endoscopic myringoplasty with temporal fascia (TF) and perichondrium (PC). Methods We conducted a retrospective comparative study that a total of 98 patients with TM perforations were included. The patients underwent endoscopic myringoplasty using PSISG, TF or PC as the graft. The closure rate, hearing outcomes, operative time and complications in three groups were compared. Results At 3 months postoperatively, the closure rate were 85.2% (23/27), 92.1% (35/38) and 87.9% (29/33) in the PSISG, TF and PC groups respectively (p = .667); Hearing improved after surgery in three groups (p < .001), and showed no significant difference among the three groups. The mean operative time of the PSISG group was shorter than autologous TF (p < .001) and PC groups (p < .001) in this study; No operative or postoperative complications were found among the three groups. Conclusion Compare to autologous temporal fascia or perichondrium, the PSISG appears to be an effective and safe material for TM perforations closure. Endoscopic PSISG myringoplasty may be an alternative technique for repairing TM perforations, especially for revision cases.