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Objectives To investigate the light penetration depth of various CAD/CAM ceramics and luting agents by spectral-domain optical coherence tomography (SD-OCT). Methods. Six CAD/CAM ceramics: lithium disilicate (LS2), zirconia-reinforced lithium silicate (ZLS), lithium aluminosilicate (LAS), polymer infiltrated (PIC), feldspar (FEL) and zirconium oxide (ZRO) and five common luting agents, two self-adhesive and three adhesive materials, were included. SD-OCT wavelengths (1310/1550 nm) and frequencies (5/28 kHz) that are particularly suitable for these materials were investigated. Subsequently, a clinical simulation was performed with an adhesively or self-adhesively inserted partial crown made of a ceramic that had an OCT penetration depth of > 1.0 mm. Results Best SD-OCT penetration was obtained at 1550 nm and 28 kHz. For ZLS, LS2 and LAS, SD-OCT light penetration depth of > 4 mm was shown. In contrast, the penetration depth of ZRO, PIC and FEL was less than 1 mm. Adhesive and self-adhesive luting agents could be visualized up to ≥ 0.9 mm. All clinically relevant areas (ceramic restoration, luting area, interfaces and adjacent tooth structures) can be imaged when SD-OCT-suitable ceramics are used. Conclusions SD-OCT can be used to analyze CAD/CAM ceramics based on ZLS, LS2 and LAS, whereas ZRO, PIC, and FEL had insufficient penetration depth for clinical application. The type of luting agent or its thickness played an insignificant role. With suitable ceramics, SD-OCT can be recommended as a non-invasive examination tool. Clinical Significance This study indicates that SD-OCT is a useful non-invasive examination method for monitoring lithium silicate-based ceramic restorations and adjacent structures.