Biofiltration of air polluted with xylene vapors was carried out for nearly two years in a large laboratory-scale installation with a volume of the bed of expanded clay equal to 32 dm3. During the experiment, different xylene inlet concentrations were applied, within the range from 300 to over 1500 mg/m3 at a linear gas flow rate of 0.008, 0.016, and 0.033 m/s, as well as 0.12 and 0.24 dm3 of medium dispensed every 3 h on top of the bed. The progress of the process was followed by measuring the xylene concentration at the inlet and outlet of the column, column mass, and gas flow resistance. The capability to purify air polluted with xylene with an average efficiency of approx. 90% was demonstrated. The process was interrupted by a significant increase in gas flow resistance, caused by a large growth of biomass, resulting in an increase in the mass of the bed by more than 45%. Both intensive rinsing of the bed with a stream of water, causing its fluidization, and rinsing and mixing after removing the bed from the column allowed to reduce flow resistance to a value close to the initial one. To ensure the supply of biogenic elements, it was necessary to periodically spray the bed with a solution of the medium in an amount of up to about 0.1 dm3/h/m3 of purified air.