Background and Objective: Clinical and population-based studies have demonstrated a strong association between obstructive sleep apnea (OSA) and cardiovascular disease (CVD). Anatomical abnormalities of the craniofacial region and upper airway are important risk factors for OSA. The objective of this study was to investigate the association of craniofacial and upper airway morphology with CVD risk biomarkers. Methods: One hundred and sixty-nine male patients with OSA underwent in-laboratory polysomnography (PSG) and upper airway computed tomography (CT) scanning. Ten-year Framingham CVD risk score (FRS) was calculated and categorized into low-and moderate-to-high-risk groups. N-terminal pro B-type natriuretic peptide (NT-proBNP) was measured as a biomarker of increased myocardial wall stress. Results: Compared to the low-risk group, total sleep time (TST), the proportion of N3 (N3%) and mean oxygen saturation (SpO(2)mean) were lower, while the arousal index of non-rapid eye movement (NREM) sleep, apnea index (AI) of NREM sleep, apnea hypopnea index (AHI) of NREM sleep, oxygen desaturation index (ODI) and percentage of total sleep time spent with oxyhemoglobin saturation below 90% (TST90) were higher in the moderate-to-high risk group. The corrected upper airway length (UAL), ANB angle and gonion-gnathion-hyoid angle were larger for subjects in the moderate-to-high risk group than those in the low-risk group. In multiple regression analysis, TST, AI(NREM) and adjusted UAL were independently associated with moderate-to-high CVD risk. Plasma NT-proBNP levels were higher in patients in the moderate-to high-risk group, and among the PSG and CT scan parameters, only SPO(2)mean was marginally associated with NT-proBNP (r=0.183, P=0.054). Conclusion: Craniofacial and upper airway features may contain valid cues about CVD risk, and sleep duration, obstructive event type and occurrence phase may be closely related to CVD risk for patients with OSA.