We systematically investigated the impact of oil droplet diameter (≈0.15, 1.6, and 11 μm) on the bioaccessibility of three oil-soluble vitamins (vitamin A palmitate, vitamin D, and vitamin E acetate) encapsulated within soybean oil-in-water emulsions stabilized by quillaja saponin. Lipid digestion kinetics decreased with increasing droplet size due to the reduction in oil–water interfacial area. Vitamin bioaccessibility decreased with increasing droplet size from 0.15 to 11 μm: 87 to 39% for vitamin A; 76 to 44% for vitamin D; 77 to 21% for vitamin E. Vitamin bioaccessibility also decreased as their hydrophobicity and molecular weight increased, probably because their tendency to remain inside the oil droplets and/or be poorly solubilized by the mixed micelles increased. Hydrolysis of the esterified vitamins also occurred under gastrointestinal conditions: vitamin A palmitate (∼90%) and vitamin E acetate (∼3%). Consequently, the composition and structure of emulsion-based delivery systems should be carefully designed when creating vitamin-fortified functional food products.