Objective: Although, the use of humidifi cation during non-invasive ventilation (NIV) is an important factor in decreasing nasal airway resistance and assuring patient's comfort and adherence; many in-vitro studies recommend switching off the humidifi er while delivering aerosol to NIV patients.The aim of the study was to in-vivo determine the effect of humidifi cation on salbutamol delivered via different inhalation devices to chronic obstructive pulmonary disease (COPD) patients using automatic continuous positive airway pressure (Auto-CPAP).Method: Aerosol delivery to NIV COPD patients by Aerogen Solo vibrating mesh nebuliser (VMN), Jet nebuliser (JET) and a metered dose inhaler (MDI) with AeroChamber MV spacer (AC) were compared with and without humidifi cation. Auto-CPAP was adjusted at non-invasive ventilation mode with the integrated heated humidifi er (IHH), as a source of humidity. The heater was set to the default setting 3, equivalent to 50ºC. Urine samples, 30 minutes and 24 hours post inhalation, as an index of the relative pulmonary and systemic bioavailability respectively, were provided by subjects and aliquots were retained for salbutamol analysis using solid phase extraction and high performance liquid chromatography (HPLC). Results:There was no signifi cant difference in the urinary excreted salbutamol post inhalation between the humidifi ed and dry conditions. However, there was a signifi cant difference between devices. The MDI with AC spacer had the highest percentage of 30 minutes urinary excreted salbutamol and JET had the lowest (p<0.01). VMN the highest percentage of 24 hours urinary excreted salbutamol and JET had the lowest but the difference was not signifi cant. Conclusion:Signifi cance of switching off humidity during aerosol delivered to ventilated patient was not as previously shown in in-vitro literatures. We recommend delivering aerosol medication to Auto-CPAP NIV patient using humidity without fear of lower delivery.