AIM: To investigate short-term changes in choroidal thickness in response to peripheral myopic defocus induced by two designs of multifocal corneal gas permeable contact lenses (MFGPCL) in young adults. METHODS: Seventeen participants, with a mean age of 24.5±4y, underwent choroidal thickness and vascularity index measurements using enhanced depth imaging optical coherence tomography (EDI OCT) at baseline, one day, and one week following MFGPCL wear. Two center-distance MFGPCL designs with similar center zone diameters of 3.0 mm but different peripheral add powers (low add: +1.5 D and high add: +3.0 D) were tested. Each participant was randomly assigned to wear one of the two MFGPCL designs. Measurements of total, luminal, and stromal choroid thickness were obtained in five eccentric regions (6 mm towards the periphery) in all quadrants. RESULTS: Significant thickening in total choroidal thickness were observed after one week of wearing both high add (+10±6 µm) and low add (+7±5 µm) MFGPCLs, with no statistically significant difference between the two groups (P=0.42). Choroidal thickening was consistent across eccentric regions and quadrants, with no significant differences based on eccentricity or quadrant (all P>0.05). Both lens designs induced choroidal thickening, with no significant difference between them in total choroidal thickness (P=0.18 for quadrants, P=0.51 for eccentric regions). CONCLUSION: Peripheral myopic defocus induced by MFGPCLs lead to significant choroidal thickening, including total, luminal, and stromal components. This study highlights the need for future research to explore the dose-response relationship between peripheral myopic defocus and choroidal thickening, utilizing choroidal response as a potential biomarker.