ObjectiveThe goal of this study was to evaluate the effects of perforation edge approximation and direct application of basic fibroblast growth factor (bFGF) each alone on the healing of large traumatic tympanic membrane perforations with inverted edges in humans.Study DesignProspective, sequential allocation, three-armed, controlled clinical study.SettingUniversity-affiliated teaching hospital.ParticipantsFifty-eight patients with large traumatic tympanic membrane perforations (i.e. affecting >50% of the surface area) with inverted edges were recruited. They were sequentially allocated to three groups: no intervention (n & 18), edge approximation alone (n & 20) and direct application of bFGF (n & 20). Otoscopy were performed before the treatment and at follow-up visits.Main outcome measuresThe closure rate, closure time and rate of otorrhoea.ResultsApplication of bFGF yielded a significantly higher average rate of perforation closure (100%) than edge approximation (60%) and no intervention (56%) (P < 0.05). It also significantly shortened the average closure time (12.4 ± 3.6 days) as compared to edge approximation (46.3 ± 8.7 days) and no intervention control (48.2 ± 5.3 days) (P < 0.05). Purulent otorrhoea was observed in none of the three groups.ConclusionEdge approximation of inverted edges has little benefit in improving the healing outcome of large traumatic tympanic membrane perforations and thus is not an ideal treatment option for large traumatic tympanic membrane perforations. Application of bFGF materially improves the closure rate of large traumatic tympanic membrane perforations and significantly shortens the closure time.