Alcohol-based hand sanitizers have been proven effective in reducing the spread of microbial infections. However, frequent use of alcohol-based formulations of hand sanitizers can cause adverse skin effects, such as allergic and irritant contact dermatitis. Thus, we evaluated the irritant potency of alcoholbased hand sanitizers containing aloe vera and clove extract with four irritation studies and compared in vivo and in vitro results. The Draize rabbit eye and skin irritancy tests were conducted to evaluate the in vivo ocular and dermal irritation potential. For in vitro evaluation of skin irritation, tissue damage was assessed with the MTT assay and by examining the release of interleukin-$1{alpha}$ (IL-$1{alpha}$) using engineered epidermal equivalents ($KeraSkin^{TM}$). A 3T3-neutral red uptake (NRU) assay was performed as a potential alternative to the Draize eye irritation test. Sanitizers containing aloe vera and clove extract were non-irritating to skin, and the results were comparable with both the in vivo and in vitro MTT viability assay. However, an increase in IL-$1{alpha}$ release was observed. The results of the in vivo eye irritation toxicity studies in rabbits demonstrated reversible conjunctival redness and edema, whereas the test article was non-irritating in the in vitro 3T3-NRU study. These data indicate that the eye is more sensitive to alcohol-based hand sanitizerinduced damage than the skin. Furthermore, in vitro tests are useful for screening purposes, but not for the elimination of in vivo testing.