AIM: To investigate the impact of multifocal gas permeable contact lens (MFGPCL) in various add power and distance/near area allocation on short-term changes of choroidal thickness (ChT), axial length (AL), and retinal defocus profile in young adults. METHODS: Seventeen young adults (2 males and 15 females; age 23.17±4.48y) were randomly assigned to wear two designs binocularly with a one-week washout period in between. Total of four MFGPCL designs were assessed. All designs were distance-center that varied in two add power (+1.50 and 3.00 D) and/or two distance zone (DZ) diameters (1.50 and 3.00 mm; design A: DZ 1.5/add 3.0, B: DZ 1.5/add 1.5, C: DZ 3.0/add 3.0, D: DZ 3.0/add 1.5). ChT, AL, and peripheral refraction data were collected on each subject at baseline, on days 1 and 7 of MFGPCL daily wear. ChT was assessed in four quadrants using a spectral-domain optical coherence tomography. RESULTS: AL was shortened by -26±44 µm with lens C, -18±27 µm with lens D, -13±29 µm with lens A, and -8±30 µm with lens B (all P<0.05). A significant overall increase in ChT was observed with all 4 designs (lens A: +6±6 µm, B: +3±7 µm, C: +8±7 µm, and D: +8±7 µm). Temporal and superior choroid exhibited more choroidal thickening associated with MFGPCL. All designs induced significant relative peripheral myopia (RPM) beyond the central 20o across the horizontal meridian in both nasal and temporal fields (P<0.05). CONCLUSION: MFGPCLs show a significant influence on ChT and AL, which are associated with significant increase in RPM after short-term wear. The reliability and feasibility of quantifying short-term changes in ChT support its use as a promising marker for the long-term efficacy of myopia-controlling treatments.