Ionic liquid (IL)-based transdermal formulations have gained significant attention because of their high skin penetration efficiency and ease of design. However, many IL-based formulations exhibit low viscosity, which hinders direct administration and leads to less efficient drug delivery. Therefore, there is a pressing need for specialized formulations with improved viscosity and efficacy as a drug delivery platform. In this study, we report a ready-to-use transdermal patch system utilizing IL-in-oil (IL/O) microemulsions to deliver acyclovir, a sparingly soluble antiviral drug. To prepare the patch system, a mixture containing equal weights of IL/O microemulsions and adhesive (Durotak 87�4098) was homogenized, subsequently coated on a liner, and covered by a support film. These patches were produced with varying thicknesses (100 μm, 200 μm, 300 μm, and 500 μm) via a solvent evaporation technique. A 24-hour in vitro skin permeation study revealed that the thinnest patch (100 μm) delivered more than 45 of the loaded drug. Drug delivery rate gradually reduced as the patch thickness increased, accounting for 22 and 14 drug permeation by 200 μm and 300 μm patches respectively. A 30-day stability study at room temperature demonstrated that neither the physical appearance nor the active ingredient content changed, validating the physical and chemical stability of the patches. Skin permeation mechanism by Fourier transform infrared spectroscopic analysis of the skin suggested that the IL/O patch possesses the capability to modify the lipid barrier in the stratum corneum thus facilitating drug diffusion. In vitro skin irritation studies on reconstructed human epidermal tissue and Yucatan micropig skin revealed that the patch exhibits no skin irritation. We believe that the adhesive nature of this newly developed IL-based patch holds significant promise as a transdermal drug delivery platform. © 2024 Elsevier B.V.