Purpose: To quantitatively characterize early emphysematous changes in the lung microstructure of current and former smokers with noninvasive helium 3 (3He) lung morphometry and to compare these results with the clinical standards, pulmonary function testing (PFT) and low-dose computed tomography (CT). Materials and Methods: This study was approved by the local institutional review board, and all subjects provided informed consent. Thirty current and former smokers, each with a minimum 30-pack-year smoking history and mild or no abnormalities at PFT, underwent 3He lung morphometry. This technique is based on diffusion MR imaging with hyperpolarized 3He gas and yields quantitative localized in vivo measurements of acinar airway geometric parameters, such as airway radii, alveolar depth, and number of alveoli per unit lung volume. These measurements enable calculation of standard morphometric characteristics, such as mean linear intercept and surface-to-volume ratio. Results: Noninvasive 3He lung morphometry was used to detect alterations in acinar structure in smokers with normal PFT findings. When compared with smokers with the largest forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio, those with chronic obstructive pulmonary disease had significantly reduced alveolar depth (0.07 mm vs 0.13 mm) and enlarged acinar ducts (0.36 mm vs 0.3 mm). The mean alveolar geometry measurements in the healthiest subjects were in excellent quantitative agreement with literature Values obtained by using invasive techniques (acinar duct radius, 0.3 mm; alveolar depth, 0.14 mm at 1 L above functional residual capacity). 3He lung morphometry depicted greater abnormalities than did PFT and CT. No adverse events were associated with inhalation of 3He gas. Conclusion: 3He lung morphometry yields valuable noninvasive insight into early emphysematous changes in alveolar geometry with increased sensitivity compared with conventional techniques.