PURPOSE: 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. MATERIALS AND METHODS: In total 875 current and former heavy smokers underwent baseline low-dose CT (30 mAs) 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 <-950 HU were categorized as representing severe emphysema (ES950), while voxels attenuated between -910 HU and -950 HU represented moderate emphysema (ES910). Impact of distribution on severity of pulmonary function impairment was investigated with logistic regression, adjusted for total amount of emphysema. RESULTS: 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). CONCLUSION: 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.