Chronic GVHD (cGVHD) remains the most important cause of late non-relapse mortality post allogeneic hematopoietic SCT (HSCT). Although first-line treatment of cGVHD with steroids is well established, evidence for second-line treatment remains limited. Here, we report a dual center retrospective analysis of the off-label salvage treatment of steroid-refractory cGVHD with everolimus. Out of 80 patients with a median age of 50 (17-70) years, 14 (17%) suffered from mild, 39 (49%) from moderate and 27 (34%) from severe cGVHD. At the final analysis, median follow-up after introduction of everolimus was 724 (14-2205) days. Thirty-four patients (43%) required the addition of further immunosuppression during everolimus-based therapy. Global NIH Severity Score improved in 34 patients (43%), remained stable in 37 patients (46%) and worsened in 9 patients (11%). The total sum of Global NIH Severity Scores in all patients assessable was significantly reduced after treatment with everolimus (P<0.0001). Most frequent grade 3/4 toxicities included infections (n=30) and thrombocytopenia (n=15). There was a single case of relapse. Everolimus-based salvage treatment of refractory cGVHD results in significant improvement of the NIH Severity Score without impairing control of the malignant disease. Finally, these preliminary results demand further verification in prospective trials.