Objective To investigate the clinical efficacy of the myringoplasty using pressed fat-patch for repairing medium- to large-sized tympanic membrane perforation under otoscope. Methods The clinical data of 52 cases (52 ears) of medium- to large-sized tympanic membrane perforation repaired by pressed fat-patch under otoscope were analyzed retrospectively, and the healing of tympanic membrane perforation as well as the improvement of hearing were investigated. Results All patients were followed up for 6~12 months. None of the 52 patients had facial paralysis, hypogustatory and other surgical complications. The total cure rate was 94.2% (49/52). The mean audiometric threshold of the patients were improved to 14.7±3.1 dB. Among them, the cure rate of 31 traumatic perforation ears was 96.8% (30/31), and the mean audiometric threshold was 14.3±1.6 dB. The cure rate of 21 ears suffered from chronic otitis was 90.5% (19/21), and the mean audiometric threshold was 15.4±4.4 dB. Conclusions The myringoplasty using pressed fat-patch for medium- to large-sized tympanic membrane perforation has reliable clinical curative effect and the high healing rate of tympanic membrane perforation. This approach is superior to the fat impaction method, which expands the clinical application of repairing tympanic membrane perforation with fat tissue.