We report a experimental design template and results of in vitro bioequivalence evaluation of 3 pMDI spacer devices tested with 3 pMDI drugs. Devices tested include MDI SpaceChamber and SpaceChamber Plus non-antistatic devices, and AeroChamber Plus Flow Vu Antistatic device. Guidelines for testing spacer devices are not clear on how many samples of each device to test, and how many replicates of each to test, and what flow rates of cascade impactor should be used. Guidelines are more clear that 3 drugs should be tested. After considerable internal debate we chose to test 6 samples of each device in triplicate to obtain suitably robust statistical measures. Further, we chose to apply 2 flow rates for NGI cascade impaction at 15 L/min and 30 L/min to approximate both child and adult inhalation rates. Normative and Cumulative aerosol size distributions were processed using validated SolAero Ltd software. From the cumulative size distributions, estimates of MMAD and GSD were calculated along with Respirable Fraction defined as aerosol within 0.5 to 4.7 um size range. Results of aerosol size metrics obtained are highly repeatable with low inter and intra variation. We conclude that experienced and skilled aerosol science technical support are important in obtaining highly repeatable results. In vitro bioanalytical data demonstrate the devices tested give comparable performance and are therefore interchangeable without the risk of delivering significantly different doses to the same patient were they to change device for another for ease of use patient choice reasons.