Recent studies have shown that near-IR (NIR) imaging methods such as NIR reflectance can be used to image lesions on proximal surfaces, and optical coherence tomography (OCT) can be used to measure the depth of those lesions below the tooth surface. These imaging modalities can be used to acquire high contrast images of demineralized tooth surfaces, and 2-D and 3-D images can be extracted from this data. At NIR wavelengths longer than 1200-nm, there is no interference from stains and the contrast is only due to the increased light scattering of the demineralization. Previous studies have shown that image-guided laser ablation can be used to remove occlusal lesions, but its use for the removal of subsurface lesions on proximal surfaces has not been investigated. The objective of this study is to demonstrate that simultaneously scanned NIR and CO2 lasers can be used to selectively remove natural and artificial interproximal caries lesions with minimal damage to sound tooth structure. In this study, images of simulated and natural interproximal lesions on extracted teeth were imaged using a digital microscope, a scanned 1460-nm superluminescent laser diode with an InGaAs detector and a cross polarization OCT system operating at 1300-nm. The lesions were subsequently removed with a CO2 laser operating at 9.3-µm and the dental handpiece and the volume of sound tissue removed was compared.