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Comprehensive management of major aphthous ulcer. Recurrent aphthous ulcers are the most prevalent oral mucosal disease, but the subset major aphthous ulcer is a less frequent type. These ulcers are refractory, may persist for several weeks to months, and interfere with the normal state of health. The aetiology is multifactorial and so is the treatment. We present a case of an adolescent male patient reported with multiple oral ulcers. He developed three ulcers simultaneously and suffered for 10 months despite using topical medications prescribed by different dental practitioners. We executed a multidisciplinary treatment approach that resulted in a long-term disease-free state. The treatment methods followed in our case could be a successful model to implement by medical practitioners and oral physicians when the situation demands.