In the present study we have shown that elastic liposome of neomycin sulphate was highly efficient in eradicating S. aureus-induced intradermal infections. The treatment with elastic liposomes neomycin sulphate applied on the skin was much more efficient than the conventional hydro-gel. The clinical implications of the data presented here suggest the possibility of substituting conventional antibiotic treatment with this novel vesicular treatment. This would result in decreased drug exposure and the associated side-effects, thereby potentially increasing patient compliance. In addition to these possible therapeutic benefits, a rapid bacterial kill and short therapy courses with elastic liposomes of neomycin sulphate could ultimately result in reducing treatment costs and minimizing bacterial resistance. These findings may open new avenues for the treatment of deep dermal infections by local application of tailored antibiotic elastic liposomes. Elastic liposomes have been studied as a possible vehicle for deep dermal delivery of neomycin sulphate, an antibacterial agent. The study confirmed that elastic liposomes are a very promising carrier for the deep dermal delivery of neomycin sulphate as revealed from an enhanced antibacterial potency, skin penetration, transdermal flux, skin deposition, and higher entrapment efficiency.