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Background-Thoracic aortic dissection (TAD) is characterized by dysregulated extracellular matrix. Little is known about the alterations of collagen and stimulators of collagen synthesis, eg, connective tissue growth factor (CTGF), in patients with TAD. In this study, we examined their roles in TAD. Methods and Results-Surgical specimens of the aortic wall of TAD patients (nϭ10) and controls (nϭ10) were tested for collagen types I and III and CTGF expression. When compared with controls, protein levels of type I and III collagen and CTGF were significantly increased by 3.2-, 3.7-, and 5.3-fold, respectively (PϽ0.05 for all). Similar patterns were shown in mRNA levels of type I␣ and I␣2 collagen and CTGF. Using immunohistochemistry and trichrome staining, we also observed elevated levels of collagen in the aortic media and adventitia. Treatment with recombinant human CTGF increased collagen synthesis in cultured aortic smooth muscle cells in a dose-and time-dependent fashion, in which expression of collagens increased from 506Ϯ108 counts per minute to 2764Ϯ240 cpm by 50 ng/mL CTGF, and from 30Ϯ43 cpm to 429Ϯ102 cpm at 48 hours. Conclusions-TAD patients exhibited significantly increased expression of aortic collagen types I and III as well as CTGF, which is likely to be responsible for the compromised aortic distensibility and systemic compliance.