Microneedles and their use as a physical skin permeation enhancement technique facilitate drug delivery across the skin in therapeutically relevant concentrations. Micropores created in the skin by MNs reseal because of normal healing processes of the skin, thus limiting the duration of the drug delivery window. Pore lifetime enhancement strategies can increase effectiveness of MNs as a drug delivery mechanism by prolonging the delivery window. Fluvastatin (FLU) was used to enhance pore lifetime by inhibiting the synthesis of cholesterol, a major component of the stratum corneum lipids. The skin recovered within a 30-45-min time period following the removal of occlusion, and there was no significant irritation observed due to the treatment compared to the control sites. Thus, it can be concluded that localized skin treatment with FLU can be used to extend micropore lifetime and deliver drugs for up to 7 days across MN-treated skin.