Background: Chronic graft-versus-host disease (cGvHD) is a major complication after allogeneic hematopoietic cell transplantation. Extracorporeal photopheresis (ECP) is an immunotherapy treatment for cGvHD, although suitable response biomarkers are lacking. Materials & methods: We analyzed data from six cGvHD patients undergoing ECP at a reference center from 826 to 2866 days. Circulating Tregs were enumerated, patient’s clinical evolution, immunosuppression dose and adverse events (AEs) registered. Results: We observed an increase in Tregs, a decrease in immunosuppression dosage and symptoms improvement. Mild AEs occurred at a very low rate. Conclusion: In these patients, the improvement of cGvHD, with low AEs, confirms a place for ECP as treatment. Improvements were accompanied by an increase in circulating Tregs, suggesting their role as a biomarker.