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Abstract Objective To evaluate the effects of fluoride (F) gels supplemented with micrometric or nano-sized sodium trimetaphosphate (TMPmicro and TMPnano, respectively) on the in vitro remineralization of caries-like lesions. Methodology Bovine enamel subsurface lesions (n=168) were selected according to their surface hardness (SH) and randomly divided into seven groups (n=24/group): Placebo (without F/TMP), 4,500 ppm F (4500F), 4500F + 2.5% TMPnano (2.5% Nano), 4500F + 5% TMPnano (5% Nano), 4500F + 5% TMPmicro (5% Micro), 9,000 ppm F (9000F), and 12,300 ppm F (Acid gel). The gels were applied in a thin layer for one minute. Half of the blocks were subjected to pH cycling for six days, whereas the remaining specimens were used for loosely- (calcium fluoride; CaF2) and firmly-bound (fluorapatite; FA) fluoride analysis. The percentage of surface hardness recovery (%SHR), area of subsurface lesion (ΔKHN), CaF2, FA, calcium (Ca), and phosphorus (P) on/in enamel were determined. Data (log10-transformed) were subjected to ANOVA and the Student-Newman-Keuls’ test (p<0.05). Results We observed a dose-response relation between F concentrations in the gels without TMP for %SHR and ΔKHN. The 2.5% Nano and 5% Micro reached similar %SHR when compared with 9000F and Acid gels. For ΔKHN, Placebo and 5% Nano gels had the highest values, and 5% Micro, 2.5% Nano, 9000F, and Acid gels, the lowest. All groups had similar retained CaF2 values, except for Placebo and Acid gel. We verified observed an increase in Ca concentrations in nano-sized TMP groups. Regarding P, TMP groups showed similar formation and retention to 9000F and Acid. Conclusion Adding 2.5% nano-sized or 5% micrometric TMP to low-fluoride gels lead to enhanced in vitro remineralization of artificial caries lesions. (F nanosized nano sized respectively carieslike like n=168 n168 n 168 (n=168 SH (SH n=24/group n24group ngroup 24 group (n=24/group) F/TMP, FTMP F/TMP , F/TMP) 4500 4 500 4,50 4500F, (4500F) 25 2 5 2.5 (2.5 Nano) (5 Micro) 9000 9 000 9,00 (9000F) 12300 12 300 12,30 gel . gel) minute days loosely CaF firmlybound firmly bound fluorapatite (fluorapatite FA analysis %SHR, SHR (%SHR) ΔKHN (ΔKHN) Ca, (Ca) P (P onin determined log10transformed logtransformed log10 transformed log (log10-transformed StudentNewmanKeuls Student Newman Keuls Student-Newman-Keuls p<0.05. p005 p p<0.05 0 05 (p<0.05) doseresponse dose response values lowest lowfluoride low n=16 n16 16 (n=16 (n=24/group 450 50 4,5 (4500F 2. (2. ( 900 00 9,0 (9000F 1230 1 30 12,3 (%SHR (ΔKHN (Ca log1 p00 p<0.0 (p<0.05 n=1 n1 (n=1 45 4, (2 90 9, 123 3 12, p0 p<0. (p<0.0 n= (n= p<0 (p<0. (n p< (p<0 (p< (p