Objectives <p>This randomized clinical trial aimed to evaluate the effect of selective caries removal in deep cavities of posterior teeth associated or not by photobiomodulation (PBM) on postoperative sensitivity, pulp vitality, and dentin neoformation.</p> Materials and methods <p>Twenty seven permanent molars with deep Class I cavities were allocated into three groups (<i>n</i> = 9): selective caries removal (Control), selective caries removal followed by infrared (IR; 810&#xa0;nm) or red (R; 660&#xa0;nm) laser irradiation. After the cavities were restored with a two-step self-etch adhesive and composite layers, the participants scored their tooth sensitivity perception on a visual analogue scale, as well as after 1, 3, and 6 months. Two teeth per group were randomly selected for cone beam computed tomography (CBCT) scanning upon restoration and after 6 months to evaluate the thickness, mineralization density, and area of neoformed dentin. The sensitivity scores among groups were statistically analyzed by the Friedman test (<i>p</i> &lt; 0.05) while dentin neoformation aspects were descriptively compared.</p> Results <p>All teeth remained vital, and the sensitivity mean scores were not significantly different among groups (<i>p</i> &lt; 0.05). Most of the CBCT sections revealed dentin neoformation in all groups. The mineralization density of affected dentin and the remaining dentin area increased in all groups, albeit higher values were found in IR and R groups.</p> Conclusion <p>Selective removal of infected dentin followed by mild self-etch adhesive application and composite restoration was effective in maintaining pulp vitality, attenuating postoperative sensitivity, and dentin neoformation after 6 months. PBM therapy improved the mineralization density and area of neoformed dentin.</p> Clinical relevance <p>Selective caries removal in deep cavities is a regenerative, effective, safe, and simplified treatment that can be combined with photobiomodulation therapy to optimize dentin neoformation.</p>