Biological markers for risk stratification of chronic GvHD (cGvHD) could improve the care of patients undergoing allogeneic hematopoietic stem cell transplantation. Increased plasma levels of B-cell activating factor (BAFF), chemokine (C-X-C motif) ligand 9 (CXCL9) and elafin have been associated with the diagnosis, but not with outcome in patients with cGvHD. We evaluated the association between levels of these soluble proteins, measured by ELISA at the time of cGvHD diagnosis and before the initiation of therapy, with non-relapse-mortality (NRM). Based on the log-transformed values, factor levels were divided into tertiles defined respectively as low, intermediate, and high levels. On univariable analysis, BAFF levels were significantly associated with NRM, whereas CXCL9 and elafin levels were not. Both low (≤2.3 ng/mL, hazard ratio (HR) = 5.8, P = 0.03) and high (>5.7 ng/mL, HR = 5.4, P = 0.03) BAFF levels were associated with a significantly higher NRM compared with intermediate BAFF level. The significant effect of high or low BAFF levels persisted in multivariable analysis. A subset of cGvHD patients had persistently low BAFF levels. In conclusion, our data show that BAFF levels at the time of cGvHD diagnosis are associated with NRM, and also are potentially useful for risk stratification. These results warrant confirmation in larger studies.