Multilayer coatings deposited by ion-beam sputtering with amorphous layers were found to have lower damage thresholds at 1064 nm than similar coatings with crystalline layers. Interestingly, at higher fluences the damage was less severe for the amorphous coatings. The magnitude of the difference in damage thresholds between the two different microstructures was strongly influenced by the size of the tested areas. To better understand the microstructure effect, single layers of HfO2 with different microstructures were studied using transmission electron microscopy, ellipsometry, and a photothermal deflection technique. Since the laser damage initiated at defects, the influence of thermal diffusivity on thermal gradients in nodular defects is also presented.