The digestion of lipophilic nutrients and micronutrients requires numerous and simultaneous processes of chemical, physical and biological nature. Studying these processes experimentally is challenging, explaining why there is only little information about the mechanisms and interactions involved. Nevertheless, the bioaccessibility of lipophilic micronutrients is poorly understood so new investigation approaches are needed, all the more when digestion of lipophilic nutrients is also involved. In this article, the development of a coarse-grained simulation with no adjustable parameter is reported, enabling the study of the chemical and physical processes controlling bioaccessibility in such systems. The intestinal digestion of a droplet of a pure triglyceride containing a lipophilic vitamin was simulated to obtain their bioaccessibility kinetics (via lipolysis and/or solubilization in bile salt). The parameters examined here were the type of triglyceride, the type of vitamin, the digestive fluid amount, the droplet size, and different digestion conditions reflecting the in vitro or in vivo cases. Among these structure and composition parameters, the type of triglyceride and the digestion conditions had the greatest effects on bioaccessibility. An interplay between triglyceride digestion and micronutrient bioaccessibility kinetics was evidenced, highlighting the roles of the different parameters, in agreement with the experimental literature. This new approach is shown to be relevant to both nutrition and pharmacology.