A 68 yr old woman presented with acute respiratory failure. She was suspected of having a phrenic-diaphragmatic impairment, without evidence of an intrinsic lung disease or generalized neuromuscular disorder, after 3 weeks of prolonged mechanical ventilation. A series of studies, including fluoroscopy, phrenic nerve stimulation test and diaphragmatic electromyography, was performed before the diagnosis of bilateral diaphragmatic paralysis (BDP) was confirmed. The patient was successfully weaned from the conventional mechanical ventilator, and was placed on nasal mask bi-level positive airway pressure (BiPAP) ventilation. A high degree of clinical suspicion of bilateral diaphragmatic paralysis should always be raised in patients suffering respiratory failure without definite predisposing factors. Weaning with noninvasive nasal mask ventilation should be tried first instead of direct tracheostomy.