Aerosol-assisted atmospheric pressure plasma allows for a one-step synthesis of vancomycin-containing nano-capsules. Morphological and chemical analyses are carried out to estimate how different discharge parameters affect the plasma deposition process. Nano-capsules size and abundance largely depend on the shell precursor content in the gas feed and on the drug concentration in the aerosol solution. Based on these results a deposition mechanism is proposed, where, interestingly, the key step is the formation of the nano-capsules in the plasma phase. Furthermore, the related antibacterial activity is proved against Staphylococcus aureus. Preliminary release tests indicate the possible exploitation of the plasma-deposited vancomycin-containing nano-capsules in the drug delivery field, and systems based on other bioactive molecules can be expected.