Objectives <p>To assess whether Steroid-Refractory chronic Graft-versus-Host Disease (SR-cGvHD) patients with oral involvement benefit from ruxolitinib regarding their clinical symptoms and oral lesions.</p> Materials and methods <p>A prospective real-life observational longitudinal patient study was conducted in patients with SR-cGVHD and oral involvement who were treated with ruxolitinib. The effects of ruxolitinib on oral lesions and symptoms were assessed 12 weeks after the start of treatment with ruxolitinib based on the complete response, partial response, and overall response rate. Additionally, oral mucosal clinical characteristics and symptoms were assessed using validated outcome scales 4 and 12 weeks after treatment.</p> Results <p>A total of 17 patients was included. Overall response rate after 12 weeks was 77%: 12% had a complete response and 65% had a partial response. A significant decrease was seen in presence of erythema (<i>p</i> = 0.002), lichenoid lesions (<i>p</i> = 0.001), median lesion site score (<i>p</i> = 0.001) and activity score (<i>p</i> = 0.001) after 12 weeks. Discomfort experienced by the patients in terms of mouth dryness, mouth pain, and mouth sensitivity was significantly ameliorated (<i>p</i> = 0.01).</p> Conclusion <p>Treatment of oral SR-cGVHD with ruxolitinib ameliorates oral lesions and symptoms experienced by patients.</p> Clinical relevance <p>: Ruxolitinib effectively treats symptoms of oral cGHVD as shown by real world evidence.</p>