Objectives: This study aims to evaluate in vivo the color agreement between natural teeth and dental shade guides by means of visual and instrumental coverage error ( $$\mathrm{CE}$$CE ) index.Materials and methods: The color of the middle third of 735 incisors was visually determined by two evaluators using the Vita Classical (VC) and Vita 3D Master (V3DM) shade guides. The color match between the natural tooth and the shade tab was rated as poor (P), good (G), or optimum (O) by each observer. CIE color coordinates of the target teeth and shade tabs of VC and V3DM were instrumentally measured using a clinical spectrophotometer. Visual ( $${\mathrm{CE}}_{\mathrm{V}}$$CEV ) and instrumental ( $${\mathrm{CE}}_{\mathrm{I}}$$CEI ) coverage error indexes were computed using CIELAB and CIEDE2000 metrics for both shade guides. For $${\mathrm{CE}}_{\mathrm{V}}$$CEV calculation, only the concordant inter-observer determination on tooth shade rated as O–O or O–G was used. The results were evaluated using perceptibility (PT, $${\mathrm{\Delta E}}_{\mathrm{ab}}^{*}$$ΔEab∗ = 1.2, $${\mathrm{\Delta E}}_{00}$$ΔE00 = 0.8) and acceptability (AT, $${\mathrm{\Delta E}}_{\mathrm{ab}}^{*}$$ΔEab∗ = 2.7, $${\mathrm{\Delta E}}_{00}$$ΔE00 = 1.8) color thresholds for dentistry.Results: VC and V3DM exhibited $${\mathrm{CE}}_{\mathrm{I}}$$CEI (2.5, 3.2, and 3.2, 2.7 CIELAB units; 1.9, 2.3, and 2.8, 2.4 CIEDE2000 units, respectively, for O–O and O–G match) and $${\mathrm{CE}}_{\mathrm{V}}$$CEV (4.7, 4.8, and 4.1, 4.6 CIELAB units; 3.3, 3.4, and 3.4, 3.6 CIEDE2000 units, respectively, for O–O and O–G match) values greater than 50:50% AT for both color difference formulas. $${\mathrm{CE}}_{\mathrm{I}}$$CEI contributes more than 50% (53.2–82.4% range) to the $${\mathrm{CE}}_{\mathrm{V}}$$CEV value. This contribution depends on the shade guide used and the quality of the visual rating.Conclusions: The evaluated shade guides exhibited visual coverage errors above acceptability thresholds, largely due to the contribution of the instrumental coverage error to the visual coverage error.Clinical relevance: It necessary to further improve commercially available dental shade guides to facilitate achievement of satisfactory esthetics results in clinical practice.