Colonization and infection of wounds represent a major reason for the impairment of tissue repair. Recently, it has been reported that tissue-tolerable plasma (TTP) is highly efficient in the reduction of the bacterial load of the skin. In the present study, the antiseptic efficacy of TTP was compared to that of octenidine hydrochloride with 2-phenoxyethanol. Both antiseptic methods proved to be highly efficient. Cutaneous treatment of the skin with octenidine hydrochloride and 2-phenoxyethanol leads to a 99% elimination of the bacteria, and 74% elimination is achieved by TTP treatment. Technical challenges with an early prototype TTP device could be held responsible for the slightly reduced antiseptic properties of TTP, compared to a standard antiseptic solution, since the manual treatment of the skin surface with a small beam of the TTP device might have led to an incomplete coverage of the treated area.