Abstract To achieve the vacuum quality required for the operation of particle accelerators, the surface of the vacuum vessels must be clean from hydrocarbons. This is usually achieved by wet chemistry processes, e.g., degreasing chemical baths that, in case of radioactive vessels, must be disposed accordingly. An alternative way exploits the oxygen plasma produced by a downstream RF plasma source. This technique offers the possibility of operating in-situ, which is an advantageous option to avoid the handling of voluminous and/or fragile components and a more sustainable alternative to large volume disposable baths. In this work, we test a commercial plasma source in dedicated vacuum systems equipped with quartz crystal microbalances (QCMs). The evolution of the etching rates of amorphous carbon (a-C) thin films deposited on the QCMs to mimic contamination are studied as function of operating parameters. We present the results of the plasma cleaning process applied to the real case of a hydrocarbons-contaminated large vacuum vessel. The studies are complemented by transport simulations and surface contamination monitoring by X-ray photoelectron spectroscopy (XPS) analysis. The evaluation of the vessel cleanliness, which is performed via residual gas analysis (RGA) measurements, is based on CERN’s outgassing acceptance criteria and agrees with both simulations and XPS results.