The aim of this study was to evaluate the remineralization effect of NaF, NaF with TCP, NaF with CPP-ACP and NaF with CXP varnishes on newly erupted first permanent molars using laser fluorescence (LF) method. The study was a randomized, double-blind, controlled trial with four parallel groups. The study was carried out in 48 high caries-risk children (DMFS >8), aged 6-7 years with newly erupted permanent first molars (initial lesion with 13 < LF value<30). A total of 140 teeth were divided randomly into four groups (n = 35): G1.Duraphat Varnish containing 5% NaF, G2. Clinpro™ White Varnish containing 5% NaF with TCP, G3.Embrace™ Varnish containing 5% NaF with CXP, G4. MI Varnish containing 5% NaF with CPP-ACP. All dental treatments of the patients were completed before the varnish application. The varnishes were applied to the targeted teeth at baseline, 1 and 3 months. Patients were called for follow-up appointments at 1, 3 and 6 months, and LF scanning was used to monitor mineralization changes. Data were analysed statistically by Wilcoxon signed-rank and Mann-Whitney U-tests. In total, 40 children (122 teeth) completed the trial. At the end of 6 months, the amount of reduction in LF values (indicating remineralization) are as follows: NaF with CXP(6.87 ± 4.32) < NaF with TCP(7.36 ± 7.05) < NaF(7.40 ± 7.03) < NaF with CPP-ACP(8.33 ± 4.90). All of the varnishes resulted in significant decrease in LF measurements and there was no significant difference between control (NaF alone) group and other groups. Only MI varnish had a significantly greater remineralization effect than Embrace™ Varnish (p < 0.05). As a non-invasive approach, CPP-ACP, TCP and CXP containing NaF varnishes have the potential to remineralize initial caries lesions on permanent first molars in high caries-risk children.