Aim of this study was to evaluate the in vitro aerosol delivery with a pressurized-metered dose inhaler and a vibrating mesh nebulizer (VMN) in heated and humidified mechanical ventilation circuits in comparison to dry circuits. Effect on drug delivery of tu rning off the heater and humidifier (HH) prior to the experiments was investigated as the influence of the position of the spacer in the circuit. Methods: A ventilator was used in volume-controlled mode with adult settings. The active HH was set at a temperature of 37°C± 2°C and a relative humidity (RH) of 100%. A filter connected to the endotracheal tube was used to collect the drug. The CombiHaler® spacer located just before the Y piece was used with both a pMDI and a VMN in heated and humidified circuits in comparison to dry circuits. Measurements were performed with both the HH turned on and off during drug administration. Aerosol delivery with the spacer located just before the HH was also evaluated in the heated and humidified circuit. Results: A decrease of aerosol delivery was observed of about 25% and 50% with respectively the VMN and the pMDI when the circuit was heated and humidified in comparison to the dry circuit. Turning off the HH prior to the experiments increased by 20% the aerosol delivery with the VMN and did not increase aerosol delivery with the pMDI. Locating the spacer just before the Y piece increased aerosol delivery.