© 2017 The Association of University Radiologists Rationale and Objective Emphysema is characterized by airspace dilation, inflammation, and irregular deposition of elastin and collagen in the interstitium. Computed tomographic studies have reported that lung mass (LM) may be increased in smokers, a finding attributed to inflammatory and parenchymal remodeling processes observed on histopathology. We sought to examine the epidemiologic and clinical associations of LM in smokers. Materials and Methods Baseline epidemiologic, clinical, and computed tomography (CT) data (n = 8156) from smokers enrolled into the COPDGene Study were analyzed. LM was calculated from the CT scan. Changes in lung function at 5 years’ follow-up were available from 1623 subjects. Regression analysis was performed to assess for associations of LM with forced expiratory volume in 1 second (FEV1) and FEV1 decline. Results Subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 chronic obstructive pulmonary disease had greater LM than either smokers with normal lung function or those with GOLD 2–4 chronic obstructive pulmonary disease (P < 0.001 for both comparisons). LM was predictive of the rate of the decline in FEV1 (decline per 100 g, −4.7 ± 1.7 mL/y, P = 0.006). Conclusions Our cross-sectional data suggest the presence of a biphasic radiological remodeling process in smokers: the presence of such nonlinearity must be accounted for in longitudinal computed tomographic studies. Baseline LM predicts the decline in lung function.