High-pressure homogenization is a widely used process in the food, pharmaceutical, and cosmetic industry for producing emulsions. Because of small dimensions and high velocities, the experimental and numerical investigation of such a process is challenging. Hence, the development of products is mostly based on trial and error. In this paper, simulations of a generic high-pressure homogenization process using the Lagrangian, mesh-free smoothed particle hydrodynamics (SPH) method are presented and compared to experimental findings using Micro-Particle Image Velocimetry (μ-PIV). The SPH code has been developed and validated with the scope of simulating technical relevant multi-phase problems (Höfler et al. 2012). The present simulations cover the investigation of two different dynamic viscosities of the dispersed phase as well as different droplet trajectories. The comparison between the simulations and the experiments focusses on the velocity distribution of the continuous phase and the droplet deformation and breakup. In both cases a qualitatively good agreement is observed, demonstrating the ability of our SPH implementation for simulating technical relevant two-phase flows.