Caffeine is the most widely consumed bioactive ingredient in the world, which has been found to show great therapeutic potential in several posterior eye diseases. While intravitreal injection represents the ideal administration route for these disorders, it remains challenging to achieve sustained release of caffeine in the vitreous. Herein, we address this issue by loading crystalline caffeine within oleogels (Ca@oleogels), oily delivery vehicles which provide a hydrophobic environment that is opposite to the hydrophilic nature of their cargos. Mathematical modeling of the in vitro release profiles indicated the diffusion process of the drug from Ca@oleogels was playing a dominating role in caffeine release. Furthermore, sustained intravitreal delivery was evidenced by higher drug levels from 12 h until the end of the pharmacokinetic study (240 h) and a 3.2-fold reduction in C