Rapid and efficient decontamination of the skin is a major task for emergency rescue services in the event of a chemical accident involving humans. While rinsing the skin with water (and soap) has been the standard procedure, some skepticism has developed in recent years regarding the situational suitability of this method. The efficacy of three different decontamination materials/techniques (Easyderm® cleaning cloth, water-soaked all-purpose sponge, rinsing with water) in removing Capsaicin, Bromadiolone, Paraquat and 2,2′-dichlorodiethylether (DCEE) from porcine skin was compared. Different cleaning motions (wiping, twisting, pressing) with the Easyderm® were evaluated for their effectiveness in removing Capsaicin from porcine skin. Finally, the impact of different exposure times of the skin to Capsaicin on the decontamination process were investigated. Contaminant recovery rates (CRRs) were analysed in the skin and in each decontamination material using high-performance-liquid-chromatography (HPLC; used for Capsaicin, Bromadiolone, Paraquat) or gas chromatography (GC; used for DCEE). Wiping the skin with the amphiphilic Easyderm® was most effective for decontamination of Capsaicin and DCEE, while the water rinsing method gave the best results for removing Paraquat and Bromadiolone. Both wiping with the Easyderm® and rotating the Easyderm® were significantly more effective in cleaning Capsaicin-contaminated skin than pressing the Easyderm® on the contamination area alone. Prolonged exposure times of the porcine skin to Capsaicin were associated with a decrease in efficacy of the following decontamination. Emergency rescue services should have materials available that can remove both hydrophilic and hydrophobic substances from skin. Since not all of our results for comparing different decontamination materials were as distinct as we expected, there are likely several other factors determining the efficacy of skin decontamination in some cases. Time is key; therefore, first responders should try to begin the decontamination process as soon as possible after arriving at the scene.