An adsorption-based biogas cleaning system for deep desulfurization (< 0.25 ppmv sulfur) was tested at pilot scale during a long-duration (1130 h) field demonstration. The goal was to protect a catalytic methanation reactor during direct methanation of biogas, where the biogas source was partly from a wastewater treatment plant and partly from a biowaste digester at a site in Switzerland. A two-vessel gas adsorptive process was used, where the first vessel focused on removal of H2S and the second vessel focused on removal of other trace sulfur compounds. The H2S sorbent used successfully removed H2S to below the 0.2 ppmv limit of quantification over the full operation hours, even in the presence of moisture and trace organic compounds (terpenes, siloxanes, etc.) in the biogas. Polishing non-H2S sulfur compounds proved more difficult, especially due to the moisture in the biogas and to the significant presence of the volatile compound dimethyl sulfide (DMS). DMS was the most difficult compound to remove and the first to break through, requiring a specific sorbent choice as well as active biogas dehumidification for best removal performance. Siloxanes were not detected after this gas cleaning stage, and terpenes were also removed. Because the sensitivity of catalytic methanation to biogas contaminants is similar to that of high temperature fuel cells, results presented here are also relevant to fuel cell applications.