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Objectives: To assess the effect of inter-proximal enamel reduction (IPR) on interradicular bone volume and incisal inclination in patients undergoing clear aligner therapy (CAT)., Materials and Methods: The study sample consisted of 60 cases which underwent orthodontic CAT, in a private clinic in Dammam, KSA. A total of 120 CBCT scans (60 pre-treatment and 60 post- treatment) were measured using the CS 3D Imaging software to examine bone volume (using height, width, and depth of the interproximal area) and incisal inclination. The corresponding ClinCheck models were collected to determine the amount and locations of interproximal reduction performed. Little's Irregularity Index values were measured using OrthoCAD software. Paired sample t-test was used to address the measurements of bone height, width, depth, bone volume, and inclination of upper and lower incisors before and after IPR., Results: IPR did not affect the upper or lower bone volume except at LR3-2 and UL 2 - 1 where a significant difference between the bone volume with and without IPR was detected (p = 0.02 and p = 0.04 respectively). Upper and lower incisor inclination showed a statistically significant decrease after IPR. There was no correlation between IPR and bone volume difference between upper and lower teeth except at LR3-2 and UL 2 - 1., Conclusions: IPR had no significant effect on inter-radicular bone volume except at areas of lower right canine-lateral and at areas of upper left central-lateral. There was a positive correlation between the amount of IPR and incisal inclination., Clinical Relevance: The current study findings suggest that while IPR has a minimal and localized effect on bone volume in certain areas, it plays a role in adjusting incisal inclination, highlighting its significance in the careful planning of orthodontic treatment using clear aligners., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)