A chronic obstructive pulmonary disease (COPD) exsmoker underwent pulmonary function tests and hyperpolarized helium-3 (3He) magnetic resonance imaging (MRI) serially over 4 years, twice prior to and twice following an acute exacerbation (AE). About 2.5 years pre-AE, 3He ventilation defect percent (VDP) was 16%, the apparent diffusion coefficient (ADC) was 0.34 cm2/s, and forced expiratory volume in 1 sec (FEV1) was 41%pred. Six months pre-AE, VDP and ADC were worse (29% and 0.38 cm2/s, respectively) without worsening FEV1 (47%pred). After hospitalization and AE treatment, VDP was 20%, whereas FEV1 did not improve (45%pred); 16 months post-AE, both VDP and ADC remained improved and similar to 4 years prior. J. Magn. Reson. Imaging 2013;37:1223–1227. © 2012 Wiley Periodicals, Inc.