Introduction: The present study aims to assess the microshear bond strength (μ SBS) of composite to enamel treated with titanium tetrafluoride (TiF4) and CO2 laser irradiation. Methods: Fifteen human molars were sectioned and their enamel surfaces were abraded. The sections were randomly assigned to 5 groups (n = 15): (CO); control group, (AP); treated with 1. 23% acidulated phosphate fluoride (APF) for 4 minutes, (Ti); 4% TiF4 for 1 minute, (L+AP); CO2 laser irradiation (10. 6 μ m wavelength, 1 W peak power, 10 ms pulse duration, 500 ms repetition time, 0. 2 mm beam spot size at the tissue level, 2 cm distance of handpiece tip to tissue surface (DSE, South Cores) followed by 1. 23% APF, and (L+ Ti); 10. 6μ m CO2 laser irradiation followed by 4% TiF4 for one minute. Using Tygon tubes, Z250 (3M/ESPE) composite was bonded to the surface of the samples. The μ SBS of composite to enamel was measured using a microtensile testing machine after 500 thermal cycles. The data were analyzed by one-way ANOVA and the Tukey HSD test (P < 0. 05). Results: The mean μ SBS was 20. 66, 20. 21, 13. 44, 23. 01, and 10. 16 MPa in CO, AP, Ti, L+AP, and L+Ti groups respectively. Significant differences were observed between CO and Ti (P = 0. 026) and also CO and L+ Ti (P < 0. 0001). Conclusion: The application of TiF4 per se and after CO2 laser irradiation on enamel decreased the μ SBS of composite to enamel; on the other hand, APF alone and after laser irradiation did not have any adverse effect on the μ SBS of composite to enamel.