Thalidomide has reported efficacy in treating refractory idiopathic aphthous ulceration and aphthous ulceration in Behçet disease (BD). However, because of its potential teratogenicity and neurotoxicity, thalidomide must be used and monitored carefully. We report our experience of using thalidomide over the past 10 years in patients referred within our region with severe refractory aphthous ulceration, and their response to treatment and side-effects. In our experience, thalidomide works well for severe refractory aphthous ulceration, with a typical patient response reported within 4 weeks, but its use is limited by neurotoxicity. The aphthous ulceration occurring in the context of BD was more difficult to control than idiopathic aphthous ulceration.