Acid resistance of CAD/CAM resin composites. Erosion-related tooth surface loss is closely related to acid exposure, such as contact with acidic beverages or disease-related reflux. As a result, dental restorations in affected patients are also exposed to acids, which indicates that the performance and longevity of a dental restoration is impacted by the acid resistance of the individually employed restorative materials. However, unlike for ceramic materials, the acid resistance of CAD/CAM resin composites is not commonly evaluated by the manufacturers, and no standardised test methods have yet been established. Against this background, the present in vitro study aimed to examine the long-term resistance of CAD/CAM resin composites (Brilliant Crios, Cerasmart, Grandio blocs, Lava Ultimate, Shofu Block HC) against three acidic media (tonic water, acetic acid, hydrochloric acid) as well as demineralized water and to investigate potential damage mechanisms. Changes in surface roughness (Sa) were detected by confocal laser scanning microscopy (CLSM), and changes in surface hardness were measured using Vickers hardness (HV). The damage mechanisms were analysed by scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS) and micro X-ray computer tomography (µXCT). For each material, few changes in either Sa or HV were identified for at least one of the different media; for Cerasmart, the sharpest deterioration in surface properties was observed. SEM–EDS revealed leaching of barium, aluminium, and titanium from fillers in a 2 µm zone on the rough but not on the polished surface of the specimen. Within the limitations of the current study, it can be concluded that polished CAD/CAM resin composites can be recommended for clinical use in patients with erosive conditions.