Developed over six decades ago, pulmonary oscillometry has re-emerged as a noninvasive and effort-independent method for evaluating respiratory-system impedance in patients with obstructive lung disease. Here, we evaluated the relationships between hyperpolarized 3He ventilation-defect-percent (VDP) and respiratory-system resistance, reactance and reactance area (AX) measurements in 175 participants including 42 never-smokers without respiratory disease, 56 ex-smokers with chronic-obstructive-pulmonary-disease (COPD), 28 ex-smokers without COPD and 49 asthmatic never-smokers. COPD participants were dichotomized based on x-ray computed-tomography (CT) evidence of emphysema (relative-area CT-density-histogram ≤ 950HU (RA950) ≥ 6.8%). In asthma and COPD subgroups, MRI VDP was significantly related to the frequency-dependence of resistance (R5-19; asthma: ρ = 0.48, P = 0.0005; COPD: ρ = 0.45, P = 0.0004), reactance at 5 Hz (X5: asthma, ρ = −0.41, P = 0.004; COPD: ρ = −0.38, P = 0.004) and AX (asthma: ρ = 0.47, P = 0.0007; COPD: ρ = 0.43, P = 0.0009). MRI VDP was also significantly related to R5-19 in COPD participants without emphysema (ρ = 0.54, P = 0.008), and to X5 in COPD participants with emphysema (ρ = −0.36, P = 0.04). AX was weakly related to VDP in asthma (ρ = 0.47, P = 0.0007) and COPD participants with (ρ = 0.39, P = 0.02) and without (ρ = 0.43, P = 0.04) emphysema. AX is sensitive to obstruction but not specific to the type of obstruction, whereas the different relationships for MRI VDP with R5-19 and X5 may reflect the different airway and parenchymal disease-specific biomechanical abnormalities that lead to ventilation defects.