A global ban on animal experiments has been proposed. Hence, it is imperative to develop alternative models. Artificial skin models should reflect the responses of subcutaneous blood vessels and the immune system to elucidate disease and identify cosmetics' base materials. Notably, skin-irritation cascades involve disruption of the epidermal barrier and the release of proinflammatory mediators in response to chemical stimuli. Such proinflammatory factors promote angiogenesis and blood vessel permeability, as observed in irritant contact dermatitis. As an alternative to animal models, we propose a novel skin-irritation model based on a three-dimensional angiogenesis platform, in which irritated keratinocytes biochemically stimulate vascular endothelial growth factors. Our microfluidic platform hosts interactions between keratinocytes and dermal fibroblasts, which promote angiogenic sprouting. We use sodium lauryl sulfate (SLS) and steartrimonium chloride (SC) as chemical irritants. The irritative effects of SLS and SC are of particular interest due to the ubiquity of both SLS and SC in cosmetics. SLS was observed to significantly affect angiogenic performance, with increasing sprout length. Further promotion of vessel sprouting and lumen formation was observed with 10, 20, and 60 M of SC, despite its classification as nonirritating and use in supposedly safe formulations. This platform provides an alternative to animal testing as a basis for testing cosmetics and pharmaceutical substances, in addition to serving as a disease model for irritant contact dermatitis.