Purpose <p>Patients with unilateral cleft lip nasal deformity(uCLND) frequently suffer olfactory dysfunction associated with their nasal anatomical deformities, but the role conductive mechanisms play is not understood. Comparative analysis was performed in this study to evaluate diffusion of odorant-laden air in the olfactory airspace between uCLND and healthy subjects.</p> Methods <p>Retrospective computational study with individual-specific anatomically realistic three-dimensional models of 8 healthy subjects with normal nasal anatomy and 7 subjects with uCLND. Three-dimensional nasal models for all subjects were created from computed tomography images. Inspiratory simulations using computational fluid dynamics were performed at 30&#xa0;L/min to simulate turbulent sniffing conditions. Simulated transport of acetaldehyde was subsequently performed and odorant diffusion in the olfactory mucosa was calculated and compared for subjects with uCLND versus healthy control. Median and interquartile range (IQR) values, as well as p-values and effect sizes for the respective comparisons were calculated.</p> Results <p>Bilaterally, the median concentration of acetaldehyde in olfactory airspace was significantly greater in healthy group (median = 329.4pg/cm²-s; IQR = 95.6pg/cm²-s) compared to patients with uCLND (median = 15.2pg/cm²-s; IQR = 30.8pg/cm²-s), with <i>p</i> = 0.0012 and a large effect size of 0.93. Similarly, fractions of acetaldehyde diffusing in the olfactory mucosa were Healthy: median = 5.83%, IQR = 2.76% versus uCLND: median = 1.18%, IQR = 0.99%; with <i>p</i> = 0.021 and effect size of 0.71.</p> Conclusion <p>The nasal anatomic deformity associated with uCLND is substantially detrimental to transportation and diffusion of acetaldehyde in the olfactory mucosa, which can be attributed to the diminished sense of smell experienced by these patients with uCLND.</p>