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To compare the clinical efficacy of glass ionomer sealants (GIS) and resin-based sealants (RBS) applied immediately or one week after silver fluoride (SF) application to permanent molars affected by molar incisor hypomineralization (MIH) in children at high risk for caries. A total of 216 MIH-affected molars (ICDAS 1–2) from 102 children aged 6–14 years were randomly allocated to six groups: Resin- or glass ionomer–based fissure sealants were placed either one week after the application of silver fluoride or during the same clinical session. In the same-visit protocols, sealants were applied immediately after silver fluoride treatment, either following gentle blot drying with cotton or after immediate rinsing. Hypersensitivity, caries progression, and sealant retention were assessed at 1, 6, and 12 months. Hypersensitivity was evaluated using the Schiff Cold Sensitivity Scale (SCASS). Sealant performance was analyzed using modified USPHS criteria. Statistical analyses included Fisher’s Exact Test and the Friedman test. Full retention was achieved in all resin-based sealant groups, while the lowest retention rate (88.9%) was recorded in the glass ionomer sealant group applied one week after silver fluoride. Caries occurred in 2.8% of teeth and was confined to three groups: glass ionomer sealants placed one week after silver fluoride, resin-based sealants applied immediately following blot drying, and glass ionomer sealants applied immediately after rinsing. All other groups showed complete clinical success. No statistically significant differences were found among groups regarding caries prevention (p = 1.000) or sealant retention (p = 0.062). Hypersensitivity decreased significantly over time in all groups. Resin-based and glass ionomer fissure sealants placed either one week after silver fluoride application or immediately following treatment, using rinsing or blot-drying protocols, showed similar outcomes over a 12-month follow-up period in terms of caries prevention and reduction of hypersensitivity. Nonetheless, within the limitations of this study, sealants placed immediately following silver fluoride application demonstrated a greater frequency of discoloration. Both glass ionomer and resin-based fissure sealants can be successfully applied either immediately or one week following silver fluoride treatment to provide protection for MIH-affected permanent molars. NCT06641011.