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Abstract Objectives Considering the fact that resin infiltrants lack antibacterial activity, this study assessed the influence of the quaternary ammonium monomer dimethylaminohexadecyl methacrylate (DMAHDM) and amorphous calcium phosphate nanoparticles (NACP) on the physical and antibacterial properties of an experimental resin infiltrant (ERI). Methodology The following groups were established: ERI (75/25 wt.% TEGDMA/BISEMA), ERI + 2.5% DMAHDM (2.5DM), ERI + 5% DMAHDM (5DM), ERI + 2% NACP (NACP), ERI + 2.5% DMAHDM + 2% NACP (2.5DM_NACP), ERI + 5% DMAHDM + 2% NACP (5DM_NACP), and Icon® (IC), a commercial resin infiltrant. Degree of conversion (DC; n=4), sorption and solubility (SO/SOL; n=8), and contact angle (CA; n=10) tests were conducted. Biofilm biomass (BB; n=6) and bacterial metabolism (BM; n=8) were evaluated after Streptococcus mutans (UA159) cultivation for 48 h on material samples. Data were evaluated by one-way ANOVA and Tukey or Games-Howell post hoc tests (α=0.05). Results IC exhibited the highest DC, with no difference from 2.5DM and 5DM. IC showed the lowest CA. IC had the lowest SO, followed by ERI, which had the lowest SOL, with no difference from IC. 5DM_NACP showed the lowest biofilm biomass, similar to 2.5DM and 5DM. Resin infiltrants containing DMAHDM showed reduced bacterial metabolism. Conclusions DMAHDM, with or without NACP, demonstrated significant antibacterial activity, while NACP impaired DC. Both DMAHDM and NACP increased the contact angle, sorption, and solubility of the resin infiltrant, which may affect the material’s clinical performance. activity (DMAHDM (NACP ERI. . (ERI) established 75/25 7525 75 25 (75/2 wt wt. TEGDMA/BISEMA, TEGDMABISEMA TEGDMA/BISEMA , TEGDMA BISEMA TEGDMA/BISEMA) 2 5 2.5 2.5DM, 25DM DM 5DM (2.5DM) 5DM, (5DM) 2.5DM_NACP, 25DMNACP DMNACP 2.5DM_NACP (2.5DM_NACP) 5DM_NACP, 5DMNACP (5DM_NACP) Icon IC, (IC) DC (DC n=4, n4 n n=4 4 n=4) SO/SOL SOSOL SO SOL (SO/SOL n=8, n8 n=8 8 CA (CA n=10 n10 10 conducted BB (BB n=6 n6 6 BM (BM UA159 UA (UA159 samples oneway one way GamesHowell Games Howell α=0.05. α005 α α=0.05 0 05 (α=0.05) materials s performance (ERI 75/2 752 7 (75/ 2. (2.5DM (5DM (2.5DM_NACP (5DM_NACP (IC n= n=1 n1 1 UA15 (UA15 α00 α=0.0 (α=0.05 75/ (75 UA1 (UA1 α0 α=0. (α=0.0 (7 (UA α=0 (α=0. ( α= (α=0 (α= (α