Objective: In the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects. • Method: The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment. • Results: Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated. • Conclusion: The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.