Purpose: To prospectively compare apparent diffusion coefficient (ADC) measurements derived from diffusion-weighted hyperpolarized helium 3 ( 3He) magnetic resonance (MR) imaging with functional and structural findings using spirometric tests and thin-section computed tomography (CT) of the lungs in asymptomatic smokers and healthy non-smokers of similar age. Materials and: Methods: All studies were HIPAA compliant and were approved by the institutional review board. Informed consent was obtained. Ventilation and diffusion-weighted 3He MR images were obtained in healthy subjects: 11 smokers (five women, six men; mean age, 47 years ± 18 [standard deviation]; range, 23-73 years) and eight nonsmokers (<100 cigarettes in lifetime) (four women, four men; mean age, 46 years ± 16; range, 23-69 years). Mean ADC values for smokers and nonsmokers were compared with spirometric values, diffusing capacity of the lung for carbon monoxide (DLCO), age, and pack-years with Spearman rank correlation coefficient (rs) and multiple linear regression analysis. Mean ADC value and thin-section CT emphysema index of relative area less than-950 HU (RA950) were compared on a regional basis by using linear mixed-effect models. Results: Mean ADC values and number of pack-years were significantly correlated (rs = 0.60; 95% confidence interval (CI): 0.21, 1.00; P = .007); relationship remained significant after adjustment for age (P = .003). DLCO was strongly correlated with pack-years (rs = -0.63; 95% CI: -0.97, -0.29; P = .004). Negative correlations between mean ADC values and percentage predicted DLCO (rs = -0.79; 95% CI: -0.93, -0.64; P < .001) and the ratio of forced expiratory volume in 1 second to forced vital capacity (rs = -0.72; 95% CI: -0.92, -0.52; P = .001) were statistically significant. Correlations between spirometric values or RA950 and number of pack-years were not significant (.05 level). Conclusion: Correlations between mean ADC values and pulmonary function test measurements for diagnosing emphysema, especially DLCO, were statistically significant.