Background and objective: Swallowing is closely coordinated with breathing but in chronic obstructive pulmonary disease (COPD) altered synchronization may predispose patients to a breach of the upper airway protective mechanisms. However, aspiration during swallow has never been demonstrated in COPD. We examined penetration of liquid material into the airway of patients with COPD and correlated it with breathing-swallow patterns. Methods: A case-control study was performed. Patients with COPD (n = 16) were matched with normal control subjects (n = 15). Sub-mandibular videofluoroscopy was done during swallow of graduated volumes of barium to detect penetration (contrast enters the airway and may contact vocal folds) and aspiration (contrast passes glottis). Respiration was monitored simultaneously to gauge synchronisation. Hospitalisation and mortality were assessed after 36 months. Results: Penetration/aspiration scores were higher in patients with COPD (3.3 +/- 0.7 vs. 1.6 +/- 0.4 in healthy controls, p=0.03; mean +/- SE). Penetration with aspiration was observed in 4/16 patients with COPD versus 1/15 controls (p = 0.07). Penetration with or without aspiration was found in 6/16 patients (p = 0.04). Inspiration-swallow-expiration patterns were favoured in individuals with COPD (p = 0.02). Penetration/aspiration was associated with higher respiratory rates (p = 0.01), reduced hyoid elevation (p = 0.04), post swallow larynx penetration (p = 0.05) and oxygen desaturation (p = 0.01). There was a trend for the penetration/aspiration group to have an adverse outcome. Conclusions: Upper airway protective mechanisms may be flawed in COPD, possibly through reduced coordination of breathing with swallowing. This abnormality may contribute to COPD morbidity in a subgroup of patients. SUMMARY AT A GLANCE: Aspiration during swallow has never been demonstrated in COPD. Using sub-mandibular videofluoroscopy during swallow of graduated volumes of barium, we demonstrate for the first time convincing aspiration of liquid material in stable COPD. The abnormality may be associated with distinctive patterns of breathing and swallow found in COPD.