Objectives: Plasma medicine focuses on the application of cold atmospheric pressure plasmas (CAPs) in or on the human body. So far, plasmas have been used to sterilize implant materials or other thermally unstable medical products and have been applied for chemical surface modifications. This study investigates the antimicrobial effect of physical plasmas on microorganisms which cause skin infections, such as Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans, depending on the plasma source and the kind of plasma excitation used. Materials: Microorganisms were plated onto MH2 agar plates. Plasma treatment was performed using the plasma sources BLASTER MEF and kinpen 09. To investigate the antimicrobial effects, the following plasma parameters have been varied: working gas, distance from nozzle to surface, electrical power, grid spacing of treatment lines, number of treatments and work piece velocity. Results: The generated plasmas had an antimicrobial effect that depended on the chosen plasma parameters, in particular on the process gas used, the plasma power and the number of treatments performed. Thus, different reactive species were observed by optical emission spectroscopy measurement in the generated plasmas. Conclusions: The study showed that CAPs exhibit profound bactericidal and fungicidal properties in vitro. However, an important factor for the antimicrobial efficacy is the composition of the ‘chemical soup' supplied by the CAP system which can be regulated by the process gases used.