Behçet's disease (BD) is a debilitating and chronic vasculitis which can affect multiple organs. Recurrent oral aphthosis is the most common clinical feature of BD. The remarkable pain associated with painful oral ulcers can exert a major impact on the patients' quality of life. Relieving pain of these oral ulcers is an essential approach in the management of mucocutaneous lesions of BD. Non-thermal CO2 laser therapy (NTCLT) as a novel photobiomodulative approach has recently been used for significant and immediate pain reduction of some types of painful oral lesions such as recurrent aphthous stomatitis, pemphigus vulgaris, and so on. In this procedure by some considerations, the conventional CO2 laser is used as a non-surgical, non- thermal, photobiomodulative laser without any visible thermal adverse effects. In this article, we report our experiences about the analgesic effects of NTCLT on painful oral aphthous ulcers of BD. We report four cases of BD, whose painful oral aphthous ulcers were irradiated with NTCLT. Immediately after NTCLT, the pain of the lesions was significantly relieved with no visible complications. The results of this study suggest that NTCLT could be proposed as a hopeful procedure for significant and instant pain relief of oral aphthous ulcers of BD without any visible thermal adverse effects.