When setting up a simulation chamber experiment it is essential, in order to ensure meaningful results, to start with a well-controlled chemical system. Coming after the chapter dealing with the requested careful characterization of the simulation chamber, the present chapter describes the preparation of the chamber before running an experiment. It includes various chamber cleaning protocols, the preparation of a clean chamber atmosphere (the reacting mixture) and a series of protocols for blank experiments. Indeed, having a clean atmosphere in a simulation chamber, as free as possible from both particulate and gaseous impurities, is essential to ensure high quality experimental results. As it may not be possible to have a perfectly clean chamber, blank experiments are crucial to both assess chamber cleanliness, account for impurities and establish uncertainties of the observed phenomena. In the present chapter, various cleaning protocols which involve the oxidation of the impurities, dilution, temperature degradation/evaporation, but the evacuation or manual cleaning are described as well. The various techniques to generate clean gas mixture—mostly clean O 2 , N 2 or water vapor, are discussed. Finally, complementarily to the reference experiments proposed in Chap. 2 , blank experiments to characterize walls chemical inertia, chamber-dependent radical sources or the presence of water-soluble species are also described.