To assess the most influential factor for pupil diameter changes among age, illuminance, and refractive state and reestablish the optimal procedures for clinical applications based on refractive state and illuminance for different age groups.The study was an observational study (repeated measure study). Participants included 219 Korean adults aged 20 to 69 years. Pupil diameters were measured using a pupilometer under scotopic, mesopic-low, and mesopic-high lighting conditions. Factor interactions among age, illuminance, and refractive state were evaluated using mixed linear model and chi-square automated interaction detection.Illuminance mainly contributed to variations in pupil diameter of participants over 50 years, whereas the refractive state was the dominant controlling factor for the pupil variation in participants below 50 years. For more generalized application, the pupil diameter decreased with older age and brighter illuminance (P < .001, inverse correlation, all comparisons). The mean pupil diameter was significantly higher in myopes and emmetropes than in hyperopes (P < .001). Pupil diameter variation modeled using the mixed model confirmed age, illuminance, and refractive error as significant factors (P < .001).Accounting for the interactions among age, illuminance, and refractive error and establishing their hierarchical dominance can be generalized using the chi-square automated interaction detection method and mixed model. Promoting age-dependent consideration for both illuminance and refractive state is necessary when pupil diameters play significant roles in clinical and manufacturing circumstances.