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BACKGROUND Portable three-dimensional (3D) imaging system has been used for periocular measurement analysis. However, this imaging system has yet to be performed and validated for the periocular area and volume measurements. OBJECTIVES To define the upper eyelid and upper eyelid fold region through a modified landmark strategy and validate the portable 3D imaging system for area and volume measurements in this periocular region. METHODS Eighty-one healthy adult Caucasians underwent 3D facial imaging using the VECTRA M3 and VECTRA H2 3D imaging systems (Canfield Scientific, Inc., Parsippany, NJ). Subsequently, the upper eyelid and upper eyelid fold regions were selected using a modified landmark localization strategy. Then, direct measurements of area and volume were performed to assess intra-rater, inter-rater, intra-method, and inter-method reliability and compare the agreement between the two devices. RESULTS VECTRA M3 and VECTRA H2 showed high reliability on upper eyelid area measurements. Excellent intra-, inter-, and intra-method reliability agreements were observed in intra-class correlation coefficient (ICC); very good agreement in intra-rater reliability was observed in relative error of measurement (REM) and relative technical error of measurement (rTEM); and good inter- and intra-method reliability were observed in REM and rTEM. For area measurement of the upper eyelid fold, VECTRA M3 for intra-rater, inter-rater, and intra-method reliability was lower than VECTRA H2. M3 and H2 had poor intra-rater, inter-rater, and intra-method reliability for volume measurements in the upper eyelid and upper eyelid fold region. CONCLUSIONS The new portable 3D imaging system achieves excellent or very good reliability values for standardized direct measurements of the upper eyelid and upper eyelid fold region, while volume measurements seem less reliable.