Aim: This randomized, double-blind, crossover, in-situstudy, compared the efficacy of toothpastes based on hydroxyapatite (HAP; fluoride-free) or fluoride, in remineralizing molar incisor hypomineralization (MIH). Methods: Two lesion-bearing enamel blocks were produced from each of thirty extracted permanent molars diagnosed with MIH. Sixty produced blocks were randomly assigned to two groups (30/group): 20% HAP or 1450 ppm fluoride toothpaste. Each group was subdivided into, etched (n=20), with lesion surface treated with 32% phosphoric acid-etchant for 5 seconds, and unetched (n=10). Blocks were cemented into intra-oral appliances (2 blocks/appliance) worn full-time by 15 subjects. Subjects used the toothpastes in a two-phase crossover manner, lasting 14 days per phase, after one-week washout period. Baseline and post-treatment mineral density (MD) was quantified using microcomputed tomography. Results: Overall, both groups showed statistically significant (paired t-test; p<.001) net-gain when MD was compared pre-treatment and post-treatment. HAP: pre-treatment (1.716±0.315) and post-treatment (1.901±0.354), Fluoride: pre-treatment (1.962±0.363) and post-treatment (2.072±0.353). Independent t-test demonstrated a practically significantly (≥10%) higher percentage remineralization with HAP toothpaste (26.02±20.68) compared with fluoride toothpaste (14.64±9.60). Higher percentage remineralization was observed in etched than unetched samples. Conclusion: The tested toothpaste based on hydroxyapatite can remineralize MIH lesions. Pre-treating the tooth surface with acid-etchant enhanced remineralization.