Acute graft-versus-host disease (aGvHD) remains a significant complication of allogeneic hematopoietic cell transplantation, with 40% of patients failing to respond to high-dose steroids. Ruxolitinib has become the standard treatment for steroid-refractory aGvHD (SR-GvHD), but its failure in approximately one-third of cases highlights the need for alternative therapies. Mesenchymal stromal cells (MSCs), known for their immunomodulatory properties, are suggested as a treatment option, but their role in SR-GvHD remains unclear. To better understand MSC therapy outcomes, the EBMT Cellular Therapy & Immunobiology Working Party conducted a survey of centers treating >20 SR-GvHD patients with MSCs between 2007 and 2020. Data from 313 patients were analyzed, revealing a 44.5% overall response rate at day 28. Responders at day 7 had a higher likelihood of maintaining responses by day 28. Using a landmark analysis, the overall survival at 12 months, conditional on being alive at day 28, was 39.2%. Survival at 12 months was 48.6% for responders, compared to 24.4% for non-responders. Despite manufacturing variabilities, MSCs produced by academic pharma appear effective in SR-GvHD, offering a viable treatment alternative for heavily pretreated patients. These findings support further investigation of MSCs to establish standardized protocols and validate their efficacy as third-line therapy for SR-GvHD.