Background: Pulmonary artery enlargement (PAE) detected using chest computed tomography (CT) is associated with poor outcomes in chronic obstructive pulmonary disease (COPD). It is unknown whether nocturnal hypoxemia occurring in smokers, with or without COPD, obstructive sleep apnoea (OSA) or their overlap, may be associated with PAE assessed by chest CT. Methods: We analysed data from two prospective cohort studies that enrolled 284 smokers in lung cancer screening programs and completing baseline home sleep studies and chest CT scans. Main pulmonary artery diameter (PAD) and the ratio of the PAD to that of the aorta (PA:Ao ratio) were measured. PAE was defined as a PAD >= 29 mm in men and >= 27 mm in women or as a PA:Ao ratio > 0.9. We evaluated the association of PAE with baseline characteristics using multivariate logistic models. Results: PAE prevalence was 27% as defined by PAD measurements and 11.6% by the PA:Ao ratio. A body mass index >= 30 kg/m(2) (OR 2.01; 95%CI 1.06-3.78), lower % predicted of forced expiratory volume in one second (FEV1) (OR 1.03; 95%CI 1.02-1.05) and higher % of sleep time with O-2 saturation < 90% (T90) (OR 1.02; 95%CI 1.00-1.03), were associated with PAE as determined by PAD. However, only T90 remained significantly associated with PAE as defined by the PA:Ao ratio (OR 1.02; 95%CI 1.01-1.03). In the subset group without OSA, only T90 remains associated with PAE, whether defined by PAD measurement (OR 1.02; 95%CI 1.01-1.03) or PA:Ao ratio (OR 1.04; 95%CI 1.01-1.07). Conclusions: In smokers with or without COPD, nocturnal hypoxemia was associated with PAE independently of OSA coexistence.