Purpose: To assess the current evidence regarding the early caries preventive effects of CPP-ACP compared with fluorides. Materials and Methods: An electronic search from PubMed, Cochrane Library, EMBASE, Web of Science and ScienceDirect database with a complementary gray literature search for randomised controlled human clinical trials were carried out. No language restrictions were applied. Results: A total of 395 participants in 10 studies of the 600 selected studies were carefully reviewed and selected for inclusion in this meta-analysis. The pooling data of the remineralisation scores in vivo showed a weighted mean difference (WMD) in favor of CPP-ACP as compared to fluorides (WMD: -2.47; 95% confidence interval [CI]: [-3.62, -1.32]; p 0.0001). The DMFS/dmfs (decayed, missing, filled surfaces) index and the Enamel Decalcification Index (EDI) did not differ significantly between CPP-ACP and fluorides. No serious side effects associated with CPP-ACP and fluoride agents were found. Conclusion: CPP-ACP may offer a safe and efficient alternative to fluorides with less mineral content loss (laser fluorescence values) and more remineralisation of early caries lesions. In view of the inherent limitations of the included researches, high-quality, well-designed randomised controlled trials are still needed. CPP-ACP has potential utility in promoting enamel remineralisation of early caries lesions compared with fluoride. Keywords: early caries, casein phosphopeptide-amorphous calcium phosphate(CPP-ACP), fluoride, meta-analysis