Studies have found reduced myopia progression with multifocal contact lenses, albeit with an unclear mechanism behind their protective effect. It is hypothesized that the induced myopic defocus of the addition zones of the multifocal contact lenses leads to choroidal thickening and therefore inhibits eye growth. In the current study, the effect of the optical design of multifocal contact lenses on choroidal thickness was investigated. Eighteen myopic participants wore four different contact lenses ((1) single-vision lenses corrected for distance, (2) single-vision lenses with +2.50 D full-field defocus, (3) Multifocal center-distance design, (4) Multifocal center-near design, both with addition power +2.50 D) for 30 min each on their right eye. Automated analysis of the macular choroidal thickness and vitreous chamber depth were performed before and after the wear of each of the contact lenses. Peripheral refraction profiles in primary gaze were obtained using eccentric photorefraction prior to contact lens wear. Choroidal thickness and vitreous chamber depth showed no significant differences to baseline with any of the contact lenses (all p > 0.05). Choroidal thickness increased by +2.1 ± 11.1 μm with the Multifocal center-distance design, by +2.0 ± 11.1 μm with the full-field defocus lens, followed by the Multifocal center-near design with +1.6 ± 11.3 μm and the single-vision contact lens correcting for distance with +0.9 ± 11.2 μm. Multifocal contact lenses have no significant influence on choroidal thickness after short-term wear. Therefore, changes in choroidal thickness might not be the main contributor to the protective effect of multifocal contact lenses in myopia control.