High‐pressure homogenization is a commonly used process to produce emulsions with a droplet size of less than 1 μm. During the process, a pre‐emulsion is pumped with a pressure of several mega Pascal through a disruption unit, where the droplets are deformed and subsequently broken up in the turbulent area of the disruption unit. The scope of this investigation is to determine the influence of the droplet trajectory on the droplet size distribution of emulsions of different viscosity ratios or interfacial tension. Measurements of the droplet deformation prior to the droplet breakup using image‐processing tools complemented the observations. In addition, computational fluid dynamics simulations were performed to determine the stress history on the droplet trajectories. It was found that droplets on a trajectory close to the wall are more deformed when leaving the disruption unit compared to droplets on the centreline. The deformation of droplets at the edge of the jet increases downstream the disruption unit until it is finally disrupted. The simulation results support the experimental data, as it can be shown that shear and strain stresses on the trajectories close to the wall significantly exceed the stresses on the trajectories on the centreline. For an emulsion with a viscosity ratio greater than 3, droplets on a trajectory close to the wall resulted in smaller droplets and narrower droplet size distribution, while no significant influence was found for smaller viscosity ratios. Lowering the interfacial tension results in a stronger deformation, which was more pronounced for lower viscosity ratios (λ ≈ 3).