Purpose Connective tissue growth factor (CTGF) is an important mediator in several fibrotic diseases, including lung fibrosis. We investigated CTGF expression in chronic lung allograft dysfunction (CLAD) and pulmonary graft-versus-host disease (GVHD) by analyzing CTGF expression in broncho-alveolar lavage (BAL) fluid, plasma and lung tissue. Methods Sixty matched lung transplant patients were included (stable, n=20; bronchiolitis obliterans syndrome (BOS), n=20, restrictive allograft syndrome (RAS), n=20). CTGF expression was analyzed in BAL 3m post-transplant, 1y post-transplant, and at CLAD diagnosis or 2y post-transplant for stable patients. Explant lung tissue of CLAD (BOS, n=20; RAS, n=20), pulmonary GHVD (n=9), and discarded donor lungs (n=20) was immunohistochemically stained for CTGF. Results BAL CTGF protein expression was significantly higher at 3m post-transplant in patients who later developed RAS compared to stable or BOS patients (ANOVA p=0.028); while CTGF expression was similar at 1y post-transplant (ANOVA p=0.20). At CLAD diagnosis, CTGF expression was significantly increased in RAS compared to stable (p=0.0007) and BOS (p=0.042). Serial analysis revealed no difference in CTGF values between time points for stable and BOS patients (ANOVA p=0.84, p=0.92), whereas CTGF levels were significantly higher in RAS at CLAD diagnosis compared to 1y post-transplant (ANOVA p=0.029). CTGF plasma values were similar between BOS, RAS, and stable (ANOVA p=0.74). Immunohistochemistry revealed a higher percentage and intensity of CTGF positive respiratory epithelial cells in BOS and RAS lungs compared to controls (ANOVA p Conclusion Higher CTGF expression is present in BAL from RAS patients at CLAD diagnosis. Lung tissue CTGF expression is increased in end-stage RAS, BOS and pulmonary GVHD. Our results suggest a potential role for CTGF in CLAD, especially RAS, and pulmonary GVHD, which warrants further investigation of CTGF and its potential therapeutic modulation in these conditions.