The aim of this systematic review was to evaluate the incidence of white spot lesion with clear aligners. Decalcification or whit spot lesion (WSL) is a white opacity seen on smooth surfaces because of retention of bacterial plaque. Recently, there has been an increase in the number of adults seeking orthodontic treatment that is both more esthetic and more comfortable. However, there are few studies reporting the prevalence of WSL with clear aligners. Clear aligner treatment provides various advantages in maintaining oral hygiene; therefore, this systematic review was conducted of all studies that reported the frequency of white spot lesion with clear aligner therapy. Literature research was conducted on different databases electronically by using specific inclusion and exclusion criteria, two independent investigators performed data extraction and analysis. Total 9,949 records were identified. However, only three articles met the criteria that were included in this systematic review. The quality assessment for included studies showed that all three studies had low quality. It was concluded that there is an increase in WSL after clear aligner therapy according to the available evidences, however, this increase is less than that reported for conventional orthodontic fixed appliances.