Formation of a low-fat oil-in-water (O/W) nanoemulsion enriched with vitamin E using the nonionic surfactant Tween 40 is studied by means of a high-pressure homogenizer. The effect of different process variables of the emulsification process, including pressure, temperature, and concentration of the emulsifying agent, is evaluated. The relation between pressure and the obtained mean droplet diameter is derived and described by an equation which can be taken as a basis of any process design. The droplet size can be decreased by increasing the vitamin E concentration. A higher fat content slightly affects the droplet size distribution and the mean droplet diameter of the nanoemulsion, so it is recommended to use preparations of nanoemulsions with low fat contents enriched with vitamin E for dietary supplement.