Statement of problem: When performing a facially driven oral rehabilitation, the interpupillary line (IL) is usually the main reference to establish esthetic and occlusal planes (EP and OP) in a frontal view. However, literature is not conclusive yet to determine the prevalence of tilted IL in natural head position (NHP) and its possible consequences on diagnosis and treatment planning. Purpose: The aim of this study is to determine the prevalence of discrepancy between IL and real horizon (HOR) in Natural Head Position (NHP). Materials and methods: Calibrated facial photographs in NHP using an external vertical reference of 235 participants were taken. Two horizontal lines were drawn on each image (IL and HOR) and the angle between them was measured. The participants were allocated in six groups, depending on the discrepancy angle, starting from 0 to 5 degrees. Results: The discrepancy frequence between IL and HOR was: 20,4% presented 0° deviation (n=48); 30,6% presented +/-1° (n=72); 25,9% presented +/-2° (n=61); 15,3% presented +/-3° (n=36); 5,9% presented +/-4° (n=14); and 1,7% presented +/-5° (n=4). The prevalence of individuals with 2 or more degrees of discrepancy between IL and HOR in NHP (which is perceptible by the human eye) was 49% of the sample. Conclusions: Within the limitations of this study, we might conclude that almost half of the population has 2 or more degrees of discrepancy between IL and HOR in NHP, which is a risk for a inaccurate digital treatment plan when exclusively based on IL. Further research is necessary to validate these findings.