Abstract Background: Mechanical ventilation offers essential ventilatory support, while the respiratory system recovers from acute respiratory failure. Yet, invasive mechanical ventilation is associated with risks and complications that prolong the duration of mechanical ventilation andincrease the risk of death. Neuromuscular dysfunctions acquired during intensive care unit (ICU)stay are considered to be one of the important factors that impair the weaning process.The aim of this work: To evaluate the role of the neuromuscular factors responsible for difficultweaning from mechanical ventilation.Methods: The study included 19 patients with difficult weaning from mechanical ventilation fromthe Alexandria medical respiratory intensive care unit (ICU) during the period from May 2009 tillMay 2010. The selected patients included patients who need mechanical ventilation for medical reasons, Patient fulfilling the parameters for weaning, (59) with failed spontaneous breathing trial. Inthe present study EMG and sensory–motor nerve conduction study was done.Results: 26% show normal study, 63% showed moderate to severe axonal sensory–motor peripheral neuropathy and 11% showed a picture of myopathy. The study revealed that 33% of thepatients with peripheral neuropathy failed weaning trials and finally died. It is also found that drugs