Previous studies have suggested that the presence of white-spot lesion is very probable when adjacent surface is affected by cavitated lesions. This study evaluated the potential of different fluoride-releasing restorative materials in arresting enamel white-spot lesions in approximal surface in contact with them, in vitro (I) and in situ (II). White-spot lesions were formed in 240 primary enamel specimens via pH-cycling. They were put in contact with cylindrical blocks of 6 materials (): composite resin, 2 high-viscous glass ionomer cements (HVGIC), resin-modified GIC, resin-modified nanoionomer, and polyacid-modified resin. In both studies I and II, these settings were designed to simulate the contact point between the restoration and simulated approximal lesion. For study I, they were subjected to a new pH-cycling cariogenic challenge for 7 or 14 days (). For study II, a randomized double-blind in situ design was conducted in two phases (7/14 days) to promote cariogenic challenge. At the end of both studies, specimens were collected for mineral analysis by cross-sectional microhardness. Higher mineral loss was observed for lesions in contact with resin (). HVGICs were the most efficient in preventing mineral loss, whereas other materials presented an intermediate behavior. It is concluded that fluoride-releasing materials can moderately reduce white-spot lesions progression, and HVGIC can arrest enamel lesion in approximal surface in contact with them.