Purpose: To assess the effects of experimental titanium tetrafluoride (TiF4) varnish and commercial sodium fluoride (NaF) varnish with CO₂ laser on enamel hardness. Materials and Methods: Ninety human enamel samples were randomly assigned to one of the following groups: 1. control (no treatment) (CO); 2. NaF varnish (2.26%) (NF); 3. TiF₄ varnish (2.45%) (TF); 4. CO₂ laser (La); 5. NaF varnish (2.26%) with CO₂ laser (NFL); 6. TiF₄ varnish (2.45%) with CO₂ laser (TFL). Enamel surface changes were determined by Vickers microhardness (VH) test with a load of 1000 g and a dwell time of 12 s. Each sample was indented three times. Data were analysed using one-way ANOVA and Tukey's test. Results: The mean surface microhardness was 245.5 VH in the CO group, 280.3 VH in group NF, 338.7 VH group TF, 277.0 VH in group La, 345.3 VH in group NFL, and 368.0 VH in group TFL. Statistical analysis showed that groups TF, NFL, and TFL had statistically significantly higher surface hardness than the control group (p 0.05). Conclusion: The microhardness of enamel treated with TiF₄ varnish with or without laser irradiation was statistically significantly greater than that of the control group. Thus, using TiF₄ to increase enamel surface microhardness can be recommended. Keywords: CO2 laser, enamel hardness, TiF₄ varnish