Background: Microdermabrasion has recently become a popular procedure among physicians and patients, whereas few studies have assessed the efficacy of different microdermabrasion protocols nowadays applied.The objective of this study was to assess the effects of microdermabrasion, as well as to compare the effects of weekly and biweekly intervals of microdermabrasion sessions on skin biophysical parameters. Methods: Ten patients entered this randomized, investigator-blind, split face study and underwent a series of six microdermabrasion treatments. One side of the face was treated every week and the other side was treated every 2 weeks, randomly. Stratum corneum hydration, sebum secretion and skin pH measurements were taken before and after the procedure on all sessions and also 1 and 4 weeks after the last treatment. Results: After 6 sessions of microdermabrasion and following comparison to baseline, a significant decrease in sebum content and a significant increase in skin pH were observed only on the side treated with the intervals of 2 weeks. Changes in skin hydration were not significant on either side. Conclusion: Microdermabrasion may have noticeable effects on skin barrier functions. It is recommended to have 2 week interval between sessions.