The objective of this in vitro study was to evaluate whether irradiation of enamel with a novel CO2 9.3-μm shortpulsed laser using energies that enhance caries resistance influences the shear bond strength of composite resin sealants to the irradiated enamel. Seventy bovine and 240 human enamel samples were irradiated with a 9.3-μm carbon dioxide laser (Solea, Convergent Dental, Inc., Natick, MA) with four different laser energies known to enhance caries resistance or ablate enamel (pulse duration from 3 μs at 1.6 mJ/pulse to 43 μs at 14.9 mJ/pulse with fluences between 3.3 and 30.4 J/cm2, pulse repetition rate between 4.1 and 41.3 Hz, beam diameter of 0.25mm and 1-mm spiral pattern, and focus distance of 4–15 mm). Irradiation was performed Bfreehand^ or using a computerized, motor-driven stage. Enamel etching was achieved with 37% phosphoric acid (Scotchbond Universal etchant, 3M ESPE, St. Paul, MN). As bonding agent, Adper Single Bond Plus was used followed by placing Z250 Filtek Supreme flowable composite resin (both 3M ESPE). After 24 h water storage, a single-plane shear bond test was performed (UltraTester, Ultradent Products, Inc., South Jordan, UT). All laser-irradiated samples showed equal or higher bond strength than non-laser-treated controls. The highest shear bond strength values were observed with the 3-μs pulse duration/0.25-mm laser pattern (mean ± SD = 31.90 ± 2.50 MPa), representing a significant 27.4% bond strength increase over the controls (25.04 ± 2.80 MPa, P ≤ 0.0001). Two other caries-preventive irradiation (3 μs/ 1 mm and 7 μs/0.25 mm) and one ablative pattern (23 μs/ 0.25mm) achieved significantly increased bond strength compared to the controls. Bovine enamel also showed in all test groups increased shear bond strength over the controls. Computerized motor-driven stage irradiation did not show superior bond strength values over the clinically more relevant freehand irradiation. Enamel that is made caries-resistant with CO2 9.3-μm short-pulsed laser irradiation showed at least equal or significantly higher shear bond strength to pit and fissure sealants than non-laser-irradiated enamel. The risk of a sealant failure due to CO2 9.3-μm short-pulsed laser irradiation appears reduced. If additional laser ablation is required before placing a sealant, the CO2 9.3-μm enamel laser-cut showed equivalent or superior bond strength to a flowable sealant.