Excessive dynamic airway collapse (EDAC) contributes to breathlessness and reduced quality of life in individuals with emphysema. We tested a novel, portable, oral positive expiratory pressure (o-PEP) device in a patient with emphysema and EDAC. MRI revealed expiratory tracheal narrowing to 80 mm2 that increased to 170 mm2 with the o-PEP device. After 2-weeks use of the o-PEP device for 33% to 66% of activities, breathlessness, quality of life, and exertional dyspnea improved compared with minimal clinically important differences (MCID): University of California-San Diego Shortness of Breath questionnaire score declined 69 to 42 (MCID, ≥5), St. George’s Respiratory Questionnaire score decreased 71 to 27 (MCID, ≥4), and before and after the 6-minute walk test Borg score difference improved from Δ3 to Δ2 (MCID, ≥1). During the 6-minute walk test on room air without the use of the o-PEP device, oxyhemoglobin saturation declined 91% to 83%; whereas, with the o-PEP device, the nadir was 90%. Use of the o-PEP device reduced expiratory central airway collapse and improved dyspnea, quality of life, and exertional desaturation in a patient with EDAC and emphysema.