To investigate impact of distribution of computed tomography (CT) emphysema on severity of airflow limitation and gas exchange impairment in current and former heavy smokers participating in a lung cancer screening trial.In total 875 current and former heavy smokers underwent baseline low-dose CT (30mAs) in our center and spirometry and diffusion capacity testing on the same day as part of the Dutch–Belgian Lung Cancer Screening Trial (NELSON). Emphysema was quantified for 872 subjects as the number of voxels with an apparent lowered X-ray attenuation coefficient. Voxels attenuated <−950HU were categorized as representing severe emphysema (ES950), while voxels attenuated between −910HU and −950HU represented moderate emphysema (ES910). Impact of distribution on severity of pulmonary function impairment was investigated with logistic regression, adjusted for total amount of emphysema.For ES910 an apical distribution was associated with more airflow obstruction and gas exchange impairment than a basal distribution (both p<0.01). The FEV 1 /FVC ratio was 1.6% (95% CI 0.42% to 2.8%) lower for apical predominance than for basal predominance, for Tlco/V A the difference was 0.12% (95% CI 0.076–0.15%). Distribution of ES950 had no impact on FEV 1 /FVC ratio, while an apical distribution was associated with a 0.076% (95% CI 0.038–0.11%) lower Tlco/V A (p<0.001).In a heavy smoking population, an apical distribution is associated with more severe gas exchange impairment than a basal distribution; for moderate emphysema it is also associated with a lower FEV 1 /FVC ratio. However, differences are small, and likely clinically irrelevant.